Author: "Vichnou Poirier-Colame" / Language: english - Searchworks@Jio Institute Digital Library Search Results

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12 results on '"Vichnou Poirier-Colame"'

1. Upregulation of intratumoral HLA class I and peritumoral Mx1 in ulcerated melanomas

Author: Daniëlle Verver, Vichnou Poirier-Colame, Gorana Tomasic, Khadija Cherif-Rebai, Dirk J. Grunhagen, Cornelis Verhoef, Stefan Suciu, Caroline Robert, Laurence Zitvogel, and Alexander M.M. Eggermont
Subjects: melanoma, ulceration, immunohistochemistry, interferon, immune-editing, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Before the era of immune checkpoint blockade, a meta-analysis encompassing fifteen trials reported that adjuvant IFN-α significantly reduces the risk of relapse and improves survival of ulcerated melanoma (UM) with no benefit for higher doses compared to lower doses. IFNa2b affects many cell intrinsic features of tumor cells and modulates the host innate and cognate immune responses. To better understand the biological traits associated with ulceration that could explain the efficacy of prophylactic type 1 IFN, we performed immunohistochemical analysis of various molecules (major histocompatibility complex class I and class II, MX Dynamin Like GTPase 1 (MX1), inducible Nitric-Oxide Synthase (iNOS) or CD47) in two retrospective cohorts of melanoma patients, one diagnosed with a primary cutaneous melanoma (1995–2013, N = 172, among whom 49% were ulcerated melanoma (UM)) and a second one diagnosed with metastatic melanoma amenable to lymph node resection (EORTC 18952 and 18991 trials, N = 98, among whom 44% were UM). We found that primary and metastatic UM exhibit higher basal expression of MHC class I molecules, independently of Breslow thickness, histology and lymphocytic infiltration compared with NUM and that primary UM harbored higher constitutive levels of the antiviral protein Mx1 at the border of tumor beds than NUM. These findings suggest that UM expand in a tumor microenvironment where chronic exposure to type 1 IFN could favor a response to exogenous IFNs.
Published: 2019
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2. Upregulation of intratumoral HLA class I and peritumoral Mx1 in ulcerated melanomas

Author: Laurence Zitvogel, D. Verver, Vichnou Poirier-Colame, Caroline Robert, Khadija Cherif-Rebai, Gorana Tomasic, Alexander M.M. Eggermont, Stefan Suciu, Dirk J. Grünhagen, Cornelis Verhoef, and Surgery
Subjects: 0301 basic medicine, immune-editing, lcsh:Immunologic diseases. Allergy, medicine.medical_treatment, Immunology, Human leukocyte antigen, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Interferon, melanoma, Immunology and Allergy, Medicine, Original Research, business.industry, Melanoma, interferon, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immune checkpoint, Blockade, ulceration, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, immunohistochemistry, Cancer research, Immunohistochemistry, business, lcsh:RC581-607, Adjuvant, medicine.drug
Abstract: Before the era of immune checkpoint blockade, a meta-analysis encompassing fifteen trials reported that adjuvant IFN-α significantly reduces the risk of relapse and improves survival of ulcerated melanoma (UM) with no benefit for higher doses compared to lower doses. IFNa2b affects many cell intrinsic features of tumor cells and modulates the host innate and cognate immune responses. To better understand the biological traits associated with ulceration that could explain the efficacy of prophylactic type 1 IFN, we performed immunohistochemical analysis of various molecules (major histocompatibility complex class I and class II, MX Dynamin Like GTPase 1 (MX1), inducible Nitric-Oxide Synthase (iNOS) or CD47) in two retrospective cohorts of melanoma patients, one diagnosed with a primary cutaneous melanoma (1995-2013, N = 172, among whom 49% were ulcerated melanoma (UM)) and a second one diagnosed with metastatic melanoma amenable to lymph node resection (EORTC 18952 and 18991 trials, N = 98, among whom 44% were UM). We found that primary and metastatic UM exhibit higher basal expression of MHC class I molecules, independently of Breslow thickness, histology and lymphocytic infiltration compared with NUM and that primary UM harbored higher constitutive levels of the antiviral protein Mx1 at the border of tumor beds than NUM. These findings suggest that UM expand in a tumor microenvironment where chronic exposure to type 1 IFN could favor a response to exogenous IFNs.
Published: 2019

3. Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy

Author: Aurélie Perier, Michaela Semeraro, C. Gronnier, Peggy Dartigues, David Enot, Kariman Chaba, Irène Villa, Laurence Zitvogel, Vichnou Poirier Colame, Sylvie Rusakiewicz, Erika Vacchelli, Christophe Mariette, Guido Kroemer, and Diane Goéré
Subjects: Male, Pathology, medicine.medical_specialty, autophagy, Esophageal Neoplasms, Genotype, Colorectal cancer, Regulatory T cell, pattern recognition receptor, ATG16L1, Biology, CD8-Positive T-Lymphocytes, T-Lymphocytes, Regulatory, Cohort Studies, Lymphocytes, Tumor-Infiltrating, immunogenic cell death, medicine, Cytotoxic T cell, Humans, Alleles, apoptosis, FOXP3, Forkhead Transcription Factors, Chemoradiotherapy, Esophageal cancer, medicine.disease, Prognosis, Immunohistochemistry, Immunosurveillance, Gene Expression Regulation, Neoplastic, Toll-Like Receptor 4, medicine.anatomical_structure, Treatment Outcome, Oncology, Cancer research, Female, Receptors, Purinergic P2X7, CD8, Priority Research Paper
Abstract: Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy.
Published: 2015

4. NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients

Author: Serge Leyvraz, Katrin S. Reiners, Christos Christidis, Jean-Yves Blay, Jonathan M. Pitt, Marion Lambert, Aurélien Marabelle, Frédéric Vély, Alexandre Ivagnes, Jean-François Emile, Christian Auclair, Benedita Rocha, Axel Le Cesne, Loic Chaigneau, Christelle Piperoglou, Kariman Chaba, Philippe Terrier, Eric Vivier, Nicolas Isambert, Julien Adam, Sylvie Rusakiewicz, Pierre Validire, Bruno Landi, Thierry Perniceni, Laurence Zitvogel, Sarah Jegou, Sylvie Bonvalot, Michaela Semeraro, Sophie Caillat-Zucman, David Enot, Sandrine Aspeslagh, Aurélie Perier, Christophe Borg, Vichnou Poirier-Colame, Anne Berger, Alexander M.M. Eggermont, Antoine Toubert, Niels Halama, Joachim Koch, Elke Pogge von Strandmann, Olivier Mir, Julien Domont, Anne Caignard, Jean-Michel Coindre, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Institut Gustave Roussy (IGR), Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Saclay, Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service d'Immunologie [AP-HM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Microorganismes, Molécules Bioactives et Physiopathologie Intestinale (LBM-E4), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] (DHU i2B ), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Departement d'Anatomopathologie, Institut Mutualiste de Montsouris (IMM), Hellenic Open University [Patras], Département de chirurgie digestive, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Jean-bernard, Département de biologie et pathologie médicales [Gustave Roussy], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Service de Pathologie, Institut Bergonié, Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et physiologie des lymphocytes T (U1020), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Virologie et Immunologie Moléculaires, Université Francois Rabelais [Tours], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'immunologie, AP-HP Hôpital universitaire Robert-Debré [Paris], Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Equipe 11, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de médecine oncologique [Gustave Roussy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Université Paris-Sud 11 - Faculté de médecine ( UP11 UFR Médecine ), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] ( DITEP ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Microorganismes, Molécules Bioactives et Physiopathologie Intestinale ( LBM-E4 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rhumatologie, inflammation-immunopathologie- biothérapie [CHU Saint-Antoine] ( DHU i2B ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Institut Mutualiste de Montsouris ( IMM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse ( U981 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Immunologie et Cancérologie Intégratives ( CRC - Inserm U1138 ), Centre de Recherche des Cordeliers ( CRC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ), Différenciation et physiologie des lymphocytes T ( U1020 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Bergonié [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Centre of the Johannes Gutenberg University Mainz, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan), Medical Oncology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)
Subjects: 0301 basic medicine, medicine.medical_treatment, Immunology, PDGFRA, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, neoplasms, Original Research, Tumor microenvironment, GiST, business.industry, Cancer, medicine.disease, digestive system diseases, 3. Good health, Immunosurveillance, 030104 developmental biology, Imatinib mesylate, Oncology, 030220 oncology & carcinogenesis, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Tyrosine kinase
Abstract: International audience; Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST. Phenotypes based on disbalanced NKp30B/NKp30C ratio (Delta BClow) and low expression levels of NKp30A were identified in one third of patients with dismal prognosis across molecular subtypes. This Delta BClow blood phenotype was associated with a pro-inflammatory and immunosuppressive tumor microenvironment. In addition, detectable levels of the NKp30 ligand sB7-H6 predicted a worse prognosis in metastatic GIST. Soluble BAG6, an alternate ligand for NKp30 was associated with low NKp30 transcription and had additional predictive value in GIST patients with high NKp30 expression. Such GIST microenvironments could be rescued by therapy based on rIFN-alpha and anti-TRAIL mAb which reinstated innate immunity.
Published: 2017
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5. Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors

Author: Jean-François Emile, Frédéric Commo, Nadege Vimond, Guido Kroemer, Axel Le Cesne, Dirk Jäger, Sylvie Rusakiewicz, Philippe Terrier, Federico Garrido, Laurence Zitvogel, Alexander M.M. Eggermont, Jean-Yves Blay, Paule Opolon, Nicolas Isambert, Valérie Le Brun-Ly, Mélanie Desbois, Patrice Dubreuil, Vichnou Poirier-Colame, Isabelle Cremer, Nathalie Chaput, Michaela Semeraro, Niels Halama, Rosa Mendez, Loic Chaigneau, Kariman Chaba, Caroline Flament, Clara Locher, Ángel Concha, Sylvie Bonvalot, Jean-Michel Coindre, Matthieu Sarabi, and Anne Caignard
Subjects: Adult, Male, Cancer Research, Stromal cell, CD3 Complex, Gastrointestinal Stromal Tumors, T-Lymphocytes, Kaplan-Meier Estimate, Biology, Piperazines, Cohort Studies, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Immune system, medicine, Humans, Protein Kinase Inhibitors, neoplasms, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, GiST, Natural Cytotoxicity Triggering Receptor 1, FOXP3, Cancer, Forkhead Transcription Factors, Middle Aged, Flow Cytometry, Prognosis, medicine.disease, Immunohistochemistry, CD56 Antigen, 3. Good health, Killer Cells, Natural, Immunosurveillance, Pyrimidines, Treatment Outcome, Imatinib mesylate, Oncology, 030220 oncology & carcinogenesis, Benzamides, Multivariate Analysis, Immunology, Imatinib Mesylate, Cancer research, Female, CD8
Abstract: Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8+ T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3+ TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3+ TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine-secreting CD56bright (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST. Cancer Res; 73(12); 3499–510. ©2013 AACR.
Published: 2013
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6. Biomarkers of immunogenic stress in metastases from melanoma patients: Correlations with the immune infiltrate

Author: Jochen T. Schaefer, Kariman Chaba, Sylvain Ladoire, David Enot, Laurence Zitvogel, Gulsun Erdag, Vichnou Poirier-Colame, Donna H. Deacon, François Ghiringhelli, Guido Kroemer, Craig L. Slingluff, Laura Senovilla, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Surgery, Division of Surgical Oncology-University of Virginia School of Medicine, Department of pathology [Virginia], University of Virginia [Charlottesville], Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institutet [Stockholm], Service de biologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), University of Virginia, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et Cancérologie Intégratives ( CRC - Inserm U1138 ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: 0301 basic medicine, Hmgb1 Expression, CD3, Immunology, T-Cells, chemical and pharmacologic phenomena, Immunogenic Cell Death, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Immune system, medicine, Autophagy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, Cell-Death, Breast-Cancer, Melanoma, Lc3b Puncta, Original Research, Hmgb1, biology, Anticancer Chemotherapy, Immune Infiltrates, Immunosurveillance, FOXP3, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Cancer research, biology.protein, Lc3, Immunogenic cell death, [SDV.IMM]Life Sciences [q-bio]/Immunology, Mechanism, Therapy, Calreticulin, CD8
Abstract: International audience; Melanoma is known to be under latent immunosurveillance. Here, we studied four biomarkers of immunogenic cell stress and death (microtubule-associated proteins 1A/1B light chain 3B (MAP-LC3B, best known as LC3B)-positive puncta in the cytoplasm as a sign of autophagy; presence of nuclear HMGB1; phosphorylation of eIF2 alpha; increase in ploidy) in melanoma cells, in tissue microarrays (TMA) from metastases from 147 melanoma patients. These biomarkers of immunogenicity were correlated with the density of immune cells infiltrating the metastases and expressing CD3, CD4(+), CD8(+), CD20, CD45, CD56, CD138, CD163, DC-LAMP or FOXP3. LC3B puncta positively correlated with the infiltration of metastases by CD163(+) macrophages, while expression of HMGB1 correlated with infiltration by FOXP3(+) regulatory T cells and CD56(+) lymphocytes. eIF2 alpha phosphorylation was associated with an augmentation of nuclear diameters, reflecting an increase in ploidy. Interestingly, therapeutic vaccination led to a reduction of eIF2 alpha phosphorylation suggestive of immunoselection against cells bearing this sign of endoplasmic reticulum (ER) stress. None of the stress/death-related biomarkers had a significant prognostic impact, contrasting with the major prognostic effect of the ratio of cytotoxic T lymphocytes (CTL) over immunosuppressive FOXP3(+) and CD163(+) cells. Altogether, these results support the idea of a mutual dialog between, on one hand, melanoma cells with their cell-intrinsic stress pathways and, on the other hand, immune effectors. Future work is required to understand the detailed mechanisms of this interaction.Keywords
Published: 2016
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7. The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer

Author: Laura Senovilla, Marie Laure Poillot, Guido Kroemer, Marie Chaix, Patrick Arveux, Fabrice Andre, Laurent Arnould, Vichnou Poirier-Colame, Laurence Zitvogel, Sylvain Ladoire, David Enot, Suzette Delaloge, François Ghiringhelli, Frédérique Penault-Llorca, Kariman Chaba, Michaela Semeraro, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe de recherche sur les traitements individualisés des cancers (ERTICa), Université d'Auvergne - Clermont-Ferrand I (UdA), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département de médecine oncologique [Gustave Roussy], Karolinska University Hospital [Stockholm], Service de biologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut Gustave Roussy ( IGR ), Immunologie et Cancérologie Intégratives ( CRC - Inserm U1138 ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe de recherche sur les traitements individualisés des cancers ( ERTICa ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
Subjects: 0301 basic medicine, Pathological Complete Response, 0302 clinical medicine, Pathology, Cytotoxic T cell, Lymphocytes, HMGB1 Protein, FOXP3, Forkhead Transcription Factors, Mammary Tumorigenesis, 3. Good health, Immunosurveillance, Death, 030220 oncology & carcinogenesis, Female, Beclin-1, Microtubule-Associated Proteins, Infiltration (medical), Histology, Predictive-Value, Breast Neoplasms, chemical and pharmacologic phenomena, Cd8, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Prognostic, 03 medical and health sciences, Immune system, Breast Cancer, medicine, Autophagy, Humans, Prognostic Value, Treg Cells, Molecular Biology, Hmgb1, Anticancer Chemotherapy, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Macrophages, Neoadjuvant Chemotherapy, Cell Biology, medicine.disease, 030104 developmental biology, Tumor progression, Cancer cell, Immunology, Cancer research, Lc3, Clinical Research Paper, CD8, T-Lymphocytes, Cytotoxic
Abstract: International audience; Several cell-intrinsic alterations have poor prognostic features in human breast cancer, as exemplified by the absence of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 )-positive puncta in the cytoplasm (which indicates reduced autophagic flux) or the loss of nuclear HMGB1 expression by malignant cells. It is well established that breast cancer is under strong immunosurveillance, as reflected by the fact that scarce infiltration of the malignant lesion by CD8(+) cytotoxic T lymphocytes or comparatively dense infiltration by immunosuppressive cell types (such as FOXP3(+) regulatory T cells or CD68(+) tumor-associated macrophages), resulting in low CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios, has a negative prognostic impact. Here, we reveal the surprising finding that cell-intrinsic features may influence the composition of the immune infiltrate in human breast cancer. Thus, the absence of LC3B puncta is correlated with intratumoral (but not peritumoral) infiltration by fewer CD8(+) cells and more FOXP3(+) or CD68(+) cells, resulting in a major drop in the CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios. Moreover, absence of HMGB1 expression in nuclei correlated with a general drop in all immune effectors, in particular FOXP3(+) and CD68(+) cells, both within the tumor and close to it. Combined analysis of LC3B puncta and HMGB1 expression allowed for improved stratification of patients with respect to the characteristics of their immune infiltrate as well as overall and metastasis-free survival. It can be speculated that blocked autophagy in, or HMGB1 loss from, cancer cells may favor tumor progression due to their negative impact on anticancer immunosurveillance.
Published: 2016
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8. Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015

Author: Erik Wennerberg, Gabriele Madonna, Gennaro Ciliberto, Michele Minopoli, Caroline Dutriaux, Matthew Wongchenko, Elisabetta Gambale, David F. Stroncek, Céleste Lebbé, Ani S. Balmanoukian, Gianluca Di Monta, Vincenzo Ingangi, Soldano Ferrone, Ivan Marquez-Rodas, Giuseppe Masucci, Janis M. Taube, Simona Mastroeni, Gerardo Bott, Franck Pagès, Jonathan M. Pitt, Judit Olasz, Elisabetta Panza, Paola Michelozzi, Daniil Stoyakovskiy, Stéphane Dalle, Mario Sznol, John M. Kirkwood, Keith T. Flaherty, Maria Capuano, Amalia Azzariti, Edward Cha, Peter Boasberg, Maria Godeny, Angela Gismondi, Ornella Franzese, Giusy Gentilcore, Jean-Jacques Grob, Olivier Michielin, Adina Elena Stanciu, Giuseppe Cirino, Julien Fourcade, Nelofer Syed, Giuseppe Ercolano, Caroline Robert, Ascierto Paolo Antonio, Christine K. Gause, Silviu Voinea, Adeeb Rahman, Anne Caignard, Camila Flores, Cristina Fortes, Yuya Yoshimoto, Angela Sandru, Andras Szollar, Monica Cantile, Frederic Lehmann, Maria Libera Ascierto, Sacha Gnjatic, Marco Tucci, Rosa Russo, Giuseppina Liguori, Valeria De Biasio, David Ross Kaufman, Mary Ruisi, Ewa Kalinka-Warzocha, Phillip Wong, Rosaria Falcon, Vincenzo Faiola, Nicole Richie, Lars Ny, Miri Blank, Paola De Cicco, Anna Passarelli, Jean-François Baurain, Guido Kroemer, Claudio Jommi, Francesca Capone, Maria Teresa Fierro, Tracee L. McMiller, Lev V. Demidov, Alessandro Testori, Omid Hamid, Marone Ugo, Annamaria Anniciello, Andrew J. Park, Fara De Murtas, RuthAnn Gordan, Emil Farkas, David Hogg, Alessandra Di Paolo, Mark Maurer, Yangyang Wang, Mario Mandalà, Rodabe N. Amaria, Massimiliano Di Marzo, Stefania Guida, Luigi Fattore, Veronica Huber, Ludmila Danilova, Luigi Aurisicchio, Gabriella Aquino, Domenico Mallardo, Catriona M. McNeil, Stephanie Anne Kronenberg, Consiglia Carella, Theresa S. Pritchard, Katia Bifulco, Michaela Semeraro, Carlo M. Croce, David P. Enot, Laurence Zitvogel, Marcella Occelli, Benjamin Weide, Magdalena Thurin, Margherita Cerrone, Naiyer A. Rizvi, Blessing Agunwamba, Stella D'Oronzo, Sarah Jegou, Stucci Stefania, Drew M. Pardoll, Vito Michele Garrisi, Haidong Tang, Szabolcs Horvath, Hong Wang, Benjamin Brady, Antonio Doronzo, Claudia Marino, Xian He, Michael A. Davies, Hexiao Wang, Isabelle Rooney, Orsolya Csuka, Maurizio Nudo, Lance Leopold, Jeffrey S. Wasser, Sabino Strippoli, Silvia Ch Formenti, MariaLaura Foddai, Michael A. Postow, Robert H.I. Andtbacka, Paul Lorigan, Tommy Andersson, Naoko Imai, Ari VanderWalde, Mariaelena Capone, Ilsung Chang, Laura Lattanzio, Carmen Loquai, Arantxa Sancho, Christine Horak, Federica Sallusto, Timea Balatoni, Maha Ayyoub, Angela Santoni, Alessio Caggiati, Anna Lisa De Presbiteris, Henrik Schmidt, Paola Savoia, Pontus Berglund, Igor Puzanov, Aurélien Marabelle, Ana Carrizossa Anderson, Hassane M. Zarour, Maria Wolodarski, Patrick Hwu, Joel Jiang, Pio Zeppa, Jeffrey A. Sosman, Eugenio Fernandez, Susan Costantini, Marcus Ballinger, Luc Thomas, Leslie Cope, Rolf Kiessling, Christophe Borg, Francesca Platini, Florian Stratica, Tilman T. Rau, Craig L. Slingluff, Paolo A. Ascierto, Angela Ianaro, Harriet M. Kluger, Stephen Hodi, Tara C. Gangadhar, Claire Vanpouille-Box, Caroline Flament, Hearn J. Cho, Mannavola Francesco, Takahiro Yamazaki, Charles G. Drake, Jason J. Luke, Miklos Kasler, Linda Pan, Caracò Corrado, Alfonso Berrocal, Angel Rivera, Vera Hirsh, Eduardo J. Patriarca, Giovanni Di Giulio, Antonello Pessi, Helena Stabile, Helene Hardy, Tucci Marco, Ralph Venhaus, Maria Luisa Di Cecilia, Catherine A. Harwood, Jonathan Cebon, Anna Maria Anniciello, Grant A. McArthur, Carlo Baldi, Ahmad A. Tarhini, Shelley Coleman, Gil Bar-Sela, Axel Hauschild, Byoung S. Kwon, Maria Paula Roberti, Sabin Cinca, Tiziana Cocco, Valeria Sorrentino, Jeffrey Wallin, Rosa Camerlingo, Sandra Demaria, Jedd D. Wolchok, Isabel Poschke, Alessandro Lugli, Michael B. Atkins, Andrea Cavalcanti, Laura Marra, Rosamaria Pinto, Adam D. Cohen, Michele Maio, Weiyi Peng, Rosario Guarrasi, David Enot, Antoni Ribas, Oscar Alabiso, Chiara Armogida, Silvestris Franco, Jessica C. Hassel, Rita Mancini, Michele Guida, Silvia C. Formenti, Andrea P. Sponghini, Imma Maida, Alba Zappalà, Charlotte M. Proby, Alan J. Korman, Yibing Yan, Matias Chacon, Haiying Xu, Carolin Blattner, Maria-Paula Roberti, Lisa Chen, James Larkin, Ryan J. Sullivan, Madonna Gabriele, Nadege Vimond, Cosmo Di Donna, Farnaz Moradi, Manish R. Patel, Sylvie Rusakiewicz, Francesca Passarelli, Luis de la Cruz-Merino, Nicolas Jacquelot, Roberta Miceli, Viktor Umansky, Akos Savolt, David Rondonotti, Gabriella Liszkay, Jianda Yuan, Stefani Spranger, Yufan Zhao, Yehuda Shoenfeld, Todd M. Bauer, Claus Garbe, Joe-Marc Chauvin, Achim A. Jungbluth, Cristiana Lo Nigro, Alexander M. Lesokhin, Gabriella Guida, Brigitte Dréno, Cindy Sanders, Jeffrey S. Weber, Janet Maleski, Chris Cheadle, Romain Daillère, Isabella Sperduti, Michaele Maio, Claudia Felici, Parneet K. Cheema, Concetta Ragone, Johan Hansson, Klara Eles, Victoria Atkinson, Speiser Daniel, Daniel O. Koralek, Zhaojun Sun, Debora Malpicci, Elena Marra, Rickard Linnskog, Jeffrey Chou, Yang Wang, Eugenia Panaitescu, F. Stephen Hodi, Anthony J. Olszanski, Chiara Botti, Nicola Mozzillo, Anna Ferretta, Paul B. Chapman, Michaë la Semeraro, Belinda Palermo, Francesco Sabbatino, Neil H. Segal, Yago Pico de Coaña, Tseng-hui Timothy Chen, Ornella Pagliano, John B. A. G. Haanen, Huibin Yue, Emilia Caputo, Alan E. Berger, Simona De Summa, Nikoletta Lendvai, Paola Queirolo, Francesco Mannavola, Thomas F. Gajewski, Michele De Tursi, Paola Nisticò, Karen Briscoe, Karmele Mujika Eizmendi, Maria Vincenza Carrier, Passarelli Anna, Laurent Mortier, Crescenzo D'Alterio, Jorge Camarero, Licia Rivoltini, Pietro Quaglino, Davide Quaresmini, Marie Vétizou, Anna Maria Di Giacomo, Chandra Prakash Prasad, Riccardo Bono, Vichnou Poirier-Colame, David Smith, Capone Mariaelena, Giosuè Scognamiglio, Margaret K. Callahan, Vashisht Gopal Yennu Nanda, Fabiola Gilda Cordaro, George J. Netto, Madalina Bolovan, Federica Fratangelo, Josep Malvehy, Robert A. Anders, Karsten A. Pilones, Vincenzo C. Battarra, Karin Leandersson, Maria Letizia Motti, Yang Xin Fu, Tim Crook, Sarah Nataraj, Alastair M. Thompson, Franco Silvestris, Carolina Cauchi, Georgina V. Long, Holbrook E Kohrt, Giuseppe Pirozzi, Celeste Fusciello, Marco Carlo Merlano, François Aubin, Mozzillo Nicola, Giuseppe Cirin, Stefania Scala, Suzanne L. Topalian, Alexander M.M. Eggermont, Antonio Marra, Jinshui Fan, Reinhard Dummer, Federica Zito Marino, Amanda Ralabate, Matthew M. Burke, Piotr Rutkowski, Gerardo Botti, Stefano Pepe, Ivor Caro, and Stefania Tommasi
Subjects: 0301 basic medicine, business.industry, MEDLINE, General Medicine, medicine.disease, Bridge (interpersonal), General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, Medical emergency, business
Published: 2016

9. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

Author: Elisabeth Chachaty, Alexander M.M. Eggermont, Vichnou Poirier-Colame, Jérôme Nigou, Antoine Roux, Gérard Eberl, Caroline Robert, Nicolas Jacquelot, Caroline Flament, Laurence Zitvogel, Franck Carbonnel, Silvia C. Formenti, Guido Kroemer, Didier Raoult, Paul Louis Woerther, Nadine Waldschmitt, David Enot, Marie Vétizou, Jonathan M. Pitt, Sonia Becharef, Romain Daillère, Christina Mateus, Sascha Cording, Paule Opolon, Sridhar Mani, Connie P.M. Duong, Nathalie Chaput, Bertrand Routy, Takahiro Yamazaki, Patricia Lepage, Ivo G. Boneca, Marion Bérard, Mathias Chamaillard, Florent Ginhoux, Sylvie Rusakiewicz, Maria Paula Roberti, Andreas Schlitzer, Encouse B. Golden, Université Paris-Sud - Paris 11 (UP11), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), New York University [New York] (NYU), NYU System (NYU), Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Albert Einstein College of Medicine [New York], Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Pôle de biologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de la Méditerranée - Aix-Marseille 2, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, La Ligue contre le cancer, ARC, Ligue Nationale contre le Cancer (Equipes labelisees), Agence Nationale pour la Recherche (ANR AUTOPH), Agence Nationale pour la Recherche (ANR, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Adoptive cell transfer, Skin Neoplasms, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], B7-H1 Antigen, Mice, Cancer immunotherapy, Bacteroides, Innate, CTLA-4 Antigen, Melanoma, Cancer, Aged, 80 and over, Multidisciplinary, Host, Antibodies, Monoclonal, hemic and immune systems, Fecal Microbiota Transplantation, Middle Aged, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Intestines, medicine.anatomical_structure, Female, Immunotherapy, Adult, T cell, T-Cells, chemical and pharmacologic phenomena, Biology, Article, Polysaccharides, medicine, Germ-Free Life, Animals, Humans, Antibody, Aged, Molecule, medicine.disease, Ipilimumab, Blockade, Gastrointestinal Microbiome, Transplantation, Mice, Inbred C57BL, CTLA-4, Immunology, Dysbiosis, Bifidobacterium, Immunologic Memory, Model
Abstract: International audience; Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, Tcell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
Published: 2015
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10. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy

Author: Aicha Goubar, Julien Adam, Joanna Cyrta, Kariman Chaba, Mireia Niso-Santano, Valentina La Sorsa, Laurence Zitvogel, Christina Pfirschke, Guido Kroemer, Gilles Uzé, Oliver Kepp, Magali Lacroix-Triki, Francesca Urbani, Antonella Sistigu, Elisa E. Baracco, Suzette Delaloge, Sylvain Ladoire, David Enot, Camilla Engblom, Marco Bianchi, Laurent Arnould, Virginie Quidville, Mauro Delorenzi, Enrico Proietti, Melvyn T. Chow, Laetitia Aymeric, Fabrice Andre, Giovanna Ziccheddu, Joachim L. Schultze, Alexander M.M. Eggermont, Thomas Tüting, Laetitia Fend, Mark J. Smyth, Catarina Remédios, Takahiro Yamazaki, Robert D. Schreiber, Laura Bracci, Erika Vacchelli, Rosa Conforti, Ilio Vitale, Paola Sestili, Mikael J. Pittet, Marie Charlotte Dessoliers, Filippo Belardelli, Vichnou Poirier-Colame, Frédérique Penault-Llorca, Jean Philippe Spano, Lajos Pusztai, Xavier Préville, Dalil Hannani, Yuting Ma, National Cancer Institute Regina Elena [Rome, Italy], Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC), Institut Gustave Roussy (IGR), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Département de biologie et pathologie médicales [Gustave Roussy], Apoptose, cancer et immunité (U848), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Life and Medical Sciences Institute for Genomics and Immunoregulation, Universität Bonn = University of Bonn, Dept. of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità (ISS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Breast Medical Oncology [Houston], The University of Texas M.D. Anderson Cancer Center [Houston], Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], UNICANCER-UNICANCER, Harvard Medical School [Boston] (HMS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Cell Biology and Neurosciences, Université Paris-Sud - Paris 11 (UP11), Sistigu, A, Yamazaki, T, Vacchelli, E, Chaba, K, Enot, Dp, Adam, J, Vitale, I, Goubar, A, Baracco, Ee, Remédios, C, Fend, L, Hannani, D, Aymeric, L, Ma, Y, Niso Santano, M, Kepp, O, Schultze, Jl, Tüting, T, Belardelli, F, Bracci, L, La Sorsa, V, Ziccheddu, G, Sestili, P, Urbani, F, Delorenzi, M, Lacroix Triki, M, Quidville, V, Conforti, R, Spano, Jp, Pusztai, L, Poirier Colame, V, Delaloge, S, Penault Llorca, F, Ladoire, S, Arnould, L, Cyrta, J, Dessoliers, Mc, Eggermont, A, Bianchi, MARCO EMILIO, Pittet, M, Engblom, C, Pfirschke, C, Préville, X, Uzè, G, Schreiber, Rd, Chow, Mt, Smyth, Mj, Proietti, E, André, F, Kroemer, G, Zitvogel, L., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), University of Bonn, Istituto Superiore di Sanità, Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Istituto Superiore di Sanita', and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Myxovirus Resistance Proteins, Messenger, Receptor, Interferon alpha-beta, Inbred C57BL, chemotherapy, Interferon alpha-beta, Mice, Interferon, Receptors, Anthracyclines, Neoplasm Metastasis, RIG-I, Pattern recognition receptor, Adaptor Proteins, General Medicine, Neoadjuvant Therapy, 3. Good health, Gene Expression Regulation, Neoplastic, Treatment Outcome, Receptors, Pattern Recognition, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Immunocompetence, medicine.drug, Receptor, Signal Transduction, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Pattern Recognition, Settore BIO/09, General Biochemistry, Genetics and Molecular Biology, Paracrine signalling, Immune system, medicine, CXCL10, Animals, Humans, cancer, RNA, Messenger, Autocrine signalling, Neoplastic, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Toll-Like Receptor 3, Mice, Inbred C57BL, Vesicular Transport, Chemokine CXCL10, Adaptor Proteins, Vesicular Transport, Gene Expression Regulation, Doxorubicin, Immunology, TLR3, RNA
Abstract: International audience; The immune system is routinely confronted with cell death resulting from the physiological turnover of renewable tissues, as well as from pathological insults of several types. We hypothesize the existence of a mechanism that allows the immune system to discriminate between physiological and pathological instances of cell death, but the factors that determine whether cellular demise is perceived as a neutral, tolerogenic or immunogenic event remain unclear 1. Infectious insults are accompanied by so-called microbe-associated molecular patterns (MAMPs), i.e., viral or bacterial products that activate immune cells through a panel of pattern-recognition receptors (PRRs) 2. Moreover, intracellular pathogens generally trigger adaptive mechanisms aimed toward the re-establishment of homeosta-sis, including the unfolded protein response (UPR) and autophagy 3,4. In mammals, MAMPs coupled to the activation of stress responses Some of the anti-neoplastic effects of anthracyclines in mice originate from the induction of innate and T cell-mediated anticancer immune responses. Here we demonstrate that anthracyclines stimulate the rapid production of type I interferons (IFNs) by malignant cells after activation of the endosomal pattern recognition receptor Toll-like receptor 3 (TLR3). By binding to IFN- and IFN- receptors (IFNARs) on neoplastic cells, type I IFNs trigger autocrine and paracrine circuitries that result in the release of chemokine (C-X-C motif) ligand 10 (CXCL10). Tumors lacking Tlr3 or Ifnar failed to respond to chemotherapy unless type I IFN or Cxcl10, respectively, was artificially supplied. Moreover, a type I IFN-related signature predicted clinical responses to anthracycline-based chemotherapy in several independent cohorts of patients with breast carcinoma characterized by poor prognosis. Our data suggest that anthracycline-mediated immune responses mimic those induced by viral pathogens. We surmise that such 'viral mimicry' constitutes a hallmark of successful chemotherapy. npg
Published: 2014
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11. Regulation of CD4+NKG2D+ Th1 Cells in Patients with Metastatic Melanoma Treated with Sorafenib: Role of IL-15Rα and NKG2D Triggering

Author: Sylvie Rusakiewicz, Sophie Caillat-Zucman, Christine Mateus, Yannick Jacques, Caroline Flament, Caroline Robert, Vichnou Poirier-Colame, Nathalie Chaput, Danila Valmori, Philippe Dessen, Philippe Vielh, Erwan Mortier, Nicolas Jacquelot, Maha Ayyoub, Camillo Porta, Laurence Zitvogel, Alexander M.M. Eggermont, Ana I. Romero, Anne Auperin, Anne Caignard, Meriem Messaoudene, Kariman Chaba, Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Laboratoire de recherche translationnelle, Direction de la recherche [Gustave Roussy], Hématopoïèse normale et pathologique (U1170 Inserm), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), IRCCS San Matteo Hospital Foundation & University of Pavia, Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université Paris-Sud - Paris 11 (UP11), This work was supported by Schering-Plough legacy, Bayer Schering Pharma, Institut National du Cancer INCa, ANR, Ligue contre le cancer (équipe labellisée de LZ) and INFLACARE EU grant, ISREC Foundation, SIRIC SOCRATES, LABEX OncoImmunology, PACRI network. S. Rusakiewicz and V. Poirier-Colame were supported by the Fondation pour la Recherche Medicale (FRM) and the Fondation de France respectively. A.I. Romero was supported by the Swedish Research Council., Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Pavia = University of Pavia (UNIPV), and Mortier, Erwan
Subjects: Male, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ligands, 0302 clinical medicine, Enzymes -- Regulation, Vemurafenib, Melanoma, Interleukin-15, 0303 health sciences, Interleukin, Middle Aged, Sorafenib, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, NK Cell Lectin-Like Receptor Subfamily K, 030220 oncology & carcinogenesis, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, CD4 antigen, Adjuvant, medicine.drug, Adult, Niacinamide, [SDV.IMM] Life Sciences [q-bio]/Immunology, Killer cells, Cells -- Growth, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Growth Processes, Young Adult, 03 medical and health sciences, Immune system, Interleukin-15 Receptor alpha Subunit, Antigen, [SDV.CAN] Life Sciences [q-bio]/Cancer, Th1 cells, medicine, Humans, Antigens, Aged, 030304 developmental biology, business.industry, Phenylurea Compounds, Th1 Cells, medicine.disease, NKG2D, Cancer research, business
Abstract: Beyond cancer-cell intrinsic factors, the immune status of the host has a prognostic impact on patients with cancer and influences the effects of conventional chemotherapies. Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents. Here, we show that a multi-tyrosine kinase inhibitor, sorafenib, upregulates interleukin (IL)-15Rα in vitro and in vivo in patients with melanoma, and in conjunction with natural killer (NK) group 2D (NKG2D) ligands, contributes to the Th1 polarization and accumulation of peripheral CD4+NKG2D+ T cells. Hence, the increase of blood CD4+NKG2D+ T cells after two cycles of sorafenib (combined with temozolomide) was associated with prolonged survival in a prospective phase I/II trial enrolling 63 patients with metastatic melanoma who did not receive vemurafenib nor immune checkpoint-blocking antibodies. In contrast, in metastatic melanoma patients treated with classical treatment modalities, this CD4+NKG2D+ subset failed to correlate with prognosis. These findings indicate that sorafenib may be used as an "adjuvant" molecule capable of inducing or restoring IL-15Rα/IL-15 in tumors expressing MHCclass I-related chain A/B (MICA/B) and on circulating monocytes of responding patients, hereby contributing to the bioactivity of NKG2D+ Th1 cells., peer-reviewed
Published: 2014
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12. Low numbers of blood and salivary natural killer cells are associated with a better response to belimumab in primary Sjögren’s syndrome: results of the BELISS study

Author: F. Desmoulins, Houria Hendel-Chavez, Thierry Lazure, Gaetane Nocturne, Philippe Ravaud, Vichnou Poirier-Colame, Raphaèle Seror, Xavier Mariette, Mohcine Benbijja, Yacine Taoufik, and Rakiba Belkhir
Subjects: Adult, T-Lymphocytes, Naive B cell, Immunology, Antibodies, Monoclonal, Humanized, Salivary Glands, Minor, Rheumatology, Interquartile range, B-Cell Activating Factor, Humans, Medicine, Immunology and Allergy, Lymphocyte Count, B-cell activating factor, B-Lymphocytes, biology, business.industry, Middle Aged, Flow Cytometry, medicine.disease, Belimumab, Sialadenitis, Killer Cells, Natural, Sjogren's Syndrome, Treatment Outcome, Monoclonal, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Rheumatism, Research Article, medicine.drug
Abstract: Introduction In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren’s syndrome (pSS) and to identify predictors of response to treatment. Methods Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index score of ≥3 points at W28. Results After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D–positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score >1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5–0.67) to 0.50 (0.5–0.5) (p=0.06). B-cell activating factor (BAFF) staining was detected in 11 (78.6 %) of 14 patients before belimumab treatment compared with 7 (50.0 %) of 14 after belimumab therapy (p=0.10). The median percentage of BAFF-positive cells in foci significantly decreased from 27.5 % (10–40) to 5 % (0–20) (p=0.03). A systemic response was achieved in six patients (40 %). The only predictor of response was the presence of a low number of natural killer (NK) cells, both in blood (8.5 % [7–10] vs 11 % [9–21]; p=0.04) and in LSG (20.6/mm3 [20.0–21.4] vs 30.0/mm3 [25.0–100.0], p=0.003). Serum BAFF levels did not influence response to treatment. Conclusions Low blood and salivary NK cell numbers are associated with a better response to belimumab. This suggests that two distinct subsets of pSS may exist: one with a predominant type I interferon (IFN)–BAFF–B-cell axis, representing good responders to belimumab; and one with a predominant type II IFN–NK cell axis, representing non-responders. Trial registration ClinicalTrials.gov identifier: NCT01160666. Registered 9 July 2010.
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12 results on '"Vichnou Poirier-Colame"'

1. Upregulation of intratumoral HLA class I and peritumoral Mx1 in ulcerated melanomas

2. Upregulation of intratumoral HLA class I and peritumoral Mx1 in ulcerated melanomas

3. Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy

4. NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients

5. Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors

6. Biomarkers of immunogenic stress in metastases from melanoma patients: Correlations with the immune infiltrate

7. The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer

8. Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015

9. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

10. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy

11. Regulation of CD4+NKG2D+ Th1 Cells in Patients with Metastatic Melanoma Treated with Sorafenib: Role of IL-15Rα and NKG2D Triggering

12. Low numbers of blood and salivary natural killer cells are associated with a better response to belimumab in primary Sjögren’s syndrome: results of the BELISS study

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