15 results on '"Maria Pérez-Lanzón"'
Search Results
2. Supplementary material from Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression
- Author
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D. Michiel Pegtel, Nicola Baldini, Tom Wurdinger, Sulev Köks, Katre Maasalu, Aare Martson, Vincenzo Canzonieri, Agostino Steffan, Silvia Cervo, Nicoletta Zini, Tanja D. de Gruijl, Sinead M. Lougheed, Roberta Bonafede, Massimo Dominici, Giulia Grisendi, Monique A.J. van Eijndhoven, Michelina Greco, Laura Roncuzzi, Ekaterina S. Jordanova, Anne-Marie Cleton-Jansen, Sonia A. Melo, Nicolas Léveillé, Xuan Dung Ho, Maria Pérez-Lanzón, Tonny Lagerweij, and S. Rubina Baglio
- Abstract
Supplementary figures and legends and supplementary tables
- Published
- 2023
3. Data from Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression
- Author
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D. Michiel Pegtel, Nicola Baldini, Tom Wurdinger, Sulev Köks, Katre Maasalu, Aare Martson, Vincenzo Canzonieri, Agostino Steffan, Silvia Cervo, Nicoletta Zini, Tanja D. de Gruijl, Sinead M. Lougheed, Roberta Bonafede, Massimo Dominici, Giulia Grisendi, Monique A.J. van Eijndhoven, Michelina Greco, Laura Roncuzzi, Ekaterina S. Jordanova, Anne-Marie Cleton-Jansen, Sonia A. Melo, Nicolas Léveillé, Xuan Dung Ho, Maria Pérez-Lanzón, Tonny Lagerweij, and S. Rubina Baglio
- Abstract
Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets.Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)–educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography.Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGFβ, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGFβ-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGFβ are increased in osteosarcoma patients.Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGFβ-blocking agents as new therapeutic options for osteosarcoma patients. Clin Cancer Res; 23(14); 3721–33. ©2017 AACR.
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- 2023
4. Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance
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Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, and Guido Kroemer
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Precocious detection ,Neuroendocrine factors ,Non-small cell lung cancer ,Immunosurveillance ,Immunotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.
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- 2024
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5. Correction: Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance
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Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, and Guido Kroemer
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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6. A Chemically Defined TLR3 Agonist with Anticancer Activity
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Julie Le Naour, Sylvain Thierry, Sarah Adriana Scuderi, Mathilde Boucard-Jourdin, Peng Liu, Marc Bonnin, Yuhong Pan, Clémence Perret, Liwei Zhao, Misha Mao, Chloé Renoux, María Pérez-Lanzón, Baptiste Martin, Oliver Kepp, Guido Kroemer, and Bettina Werlé
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Cancer immunotherapy ,dendritic cells ,formyl peptide receptor 1 ,immmunogenic cell death ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ABSTRACTToll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic – polyuridylic acid). In preclinical models, we show that TL-532 is bioavailable after parenteral injection, has an acceptable toxicological profile, and stimulates the production of multiple chemokines and interleukins that constitute pharmacodynamic markers of its immunostimulatory action. When given at a high dose, TL-532 monotherapy reduced the growth of bladder cancers growing on mice. In addition, in immunodeficient mice lacking formylpeptide receptor-1 (FPR1), TL-532 was able to restore the response of orthotopic subcutaneous fibrosarcoma to immunogenic chemotherapy. Altogether, these findings may encourage further development of TL-532 as an immunotherapeutic anticancer agent.
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- 2023
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7. A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
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Tonny Lagerweij, Maria Pérez-Lanzón, S. Rubina Baglio, Neurosurgery, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and Pathology
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0301 basic medicine ,Cancer Research ,Stromal cell ,General Chemical Engineering ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Extracellular Vesicles ,Mice ,03 medical and health sciences ,Paracrine signalling ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Osteosarcoma ,Tumor microenvironment ,General Immunology and Microbiology ,General Neuroscience ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Extracellular vesicle ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,Cancer cell ,Cancer research ,Adult stem cell - Abstract
Within the tumor microenvironment, resident or recruited mesenchymal stem cells (MSCs) contribute to malignant progression in multiple cancer types. Under the influence of specific environmental signals, these adult stem cells can release paracrine mediators leading to accelerated tumor growth and metastasis. Defining the crosstalk between tumor and MSCs is of primary importance to understand the mechanisms underlying cancer progression and identify novel targets for therapeutic intervention. Cancer cells produce high amounts of extracellular vesicles (EVs), which can profoundly affect the behavior of target cells in the tumor microenvironment or at distant sites. Tumor EVs enclose functional biomolecules, including inflammatory RNAs and (onco)proteins, that can educate stromal cells to enhance the metastatic behavior of cancer cells or to participate in the pre-metastatic niche formation. In this article, we describe the development of a preclinical cancer mouse model that enables specific evaluation of the EV-mediated crosstalk between tumor and mesenchymal stem cells. First, we describe the purification and characterization of tumor-secreted EVs and the assessment of the EV internalization by MSCs. We then make use of a multiplex bead-based immunoassay to evaluate the alteration of the MSC cytokine expression profile induced by cancer EVs. Finally, we illustrate the generation of a bioluminescent orthotopic xenograft mouse model of osteosarcoma that recapitulates the tumor-MSC interaction, and show the contribution of EV-educated MSCs to tumor growth and metastasis formation. Our model provides the opportunity to define how cancer EVs shape a tumor-supporting environment, and to evaluate whether blockade of the EV-mediated communication between tumor and MSCs prevents cancer progression.
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- 2018
8. Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression
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Anne-Marie Cleton-Jansen, Vincenzo Canzonieri, Monique A. J. van Eijndhoven, Laura Roncuzzi, Sulev Kõks, Tonny Lagerweij, Nicoletta Zini, Massimo Dominici, Maria Pérez-Lanzón, Roberta Bonafede, Tanja D. de Gruijl, Silvia Cervo, Aare Märtson, Nicolas Léveillé, D. Michiel Pegtel, Nicola Baldini, Thomas Wurdinger, Xuan Dung Ho, Agostino Steffan, Katre Maasalu, Ekaterina S. Jordanova, S. Rubina Baglio, Giulia Grisendi, M. Greco, Sonia A. Melo, Sinéad M. Lougheed, Baglio, S. Rubina, Lagerweij, Tonny, Pérez-Lanzón, Maria, Ho, Xuan Dung, Léveillé, Nicola, Melo, Sonia A., Cleton-Jansen, Anne-Marie, Jordanova, Ekaterina S., Roncuzzi, Laura, Greco, Michelina, van Eijndhoven, Monique A. J., Grisendi, Giulia, Dominici, Massimo, Bonafede, Roberta, Lougheed, Sinead M., de Gruijl, Tanja D., Zini, Nicoletta, Cervo, Silvia, Steffan, Agostino, Canzonieri, Vincenzo, Martson, Aare, Maasalu, Katre, Köks, Sulev, Wurdinger, Tom, Baldini, Nicola, Pegtel, D. Michiel, Pathology, AII - Cancer immunology, CCA - Cancer biology and immunology, Neurosurgery, Obstetrics and gynaecology, Medical oncology, Medical oncology laboratory, Amsterdam Reproduction & Development (AR&D), Baglio, S Rubina, Melo, Sonia A, Jordanova, Ekaterina S, van Eijndhoven, Monique A J, Lougheed, Sinead M, de Gruijl, Tanja D, Pegtel, D Michiel, Center of Experimental and Molecular Medicine, Other departments, and ARD - Amsterdam Reproduction and Development
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0301 basic medicine ,Male ,Cancer Research ,Pathology ,Lung Neoplasms ,Exosomes ,Mice ,Transforming Growth Factor beta ,Osteosarcoma ,Tissue microarray ,biology ,Extracellular vesicle ,Gene Expression Regulation, Neoplastic ,Mesenchymal Stem Cell ,Oncology ,EV-associated TGFβ ,Cells ,Recipient cells ,Female ,tumor extracellular vesicle (EV)–educated mesenchymal stem cells (TEMSC) ,Human ,Signal Transduction ,STAT3 Transcription Factor ,musculoskeletal diseases ,medicine.medical_specialty ,Extracellular Vesicle ,Antibodies, Monoclonal, Humanized ,Extracellular Vesicles ,tocilizumab ,03 medical and health sciences ,Stroma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cell Proliferation ,therapy ,business.industry ,Animal ,Interleukin-6 ,Mesenchymal stem cell ,Cancer ,Mesenchymal Stem Cells ,Transforming growth factor beta ,Gene signature ,medicine.disease ,Lung Neoplasm ,Exosome ,Disease Models, Animal ,030104 developmental biology ,Tissue Array Analysis ,biology.protein ,Cancer research ,Cell ,business ,Tissue Array Analysi ,osteosarcoma - Abstract
Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets. Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)–educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography. Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGFβ, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGFβ-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGFβ are increased in osteosarcoma patients. Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGFβ-blocking agents as new therapeutic options for osteosarcoma patients. Clin Cancer Res; 23(14); 3721–33. ©2017 AACR.
- Published
- 2017
9. New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma
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Carlos Lopez-Otin, Christophe Klein, Chantal Desdouets, Guido Kroemer, Pierre Laurent-Puig, Jonathan Pol, Sophie Mouillet-Richard, Gautier Stoll, Isabelle Martins, Maria Perez-Lanzon, Vincent Carbonnier, Pierre Cordier, Fatima Domenica Elisa De Palma, Adriana Petrazzuolo, Floriane Arbaretaz, Khady Mangane, Helene Fohrer Ting, Juliette Paillet, Delphine Le Corre, Wenjjin Xiao, Marine Sroussi, and Maria Chiara Maiuri
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Progress in breast cancer (BC) research relies on the availability of suitable cell lines that can be implanted in immunocompetent laboratory mice. The best studied mouse strain, C57BL/6, is also the only one for which multiple genetic variants are available to facilitate the exploration of the cancer-immunity dialog. Driven by the fact that no hormone receptor-positive (HR+) C57BL/6-derived mammary carcinoma cell lines are available, we decided to establish such cell lines.Methods BC was induced in female C57BL/6 mice using a synthetic progesterone analog (medroxyprogesterone acetate, MPA) combined with a DNA damaging agent (7,12-dimethylbenz[a]anthracene, DMBA). Cell lines were established from these tumors and selected for dual (estrogen+progesterone) receptor positivity, as well as transplantability into C57BL/6 immunocompetent females.Results One cell line, which we called B6BC, fulfilled these criteria and allowed for the establishment of invasive estrogen receptor-positive (ER+) tumors with features of epithelial to mesenchymal transition that were abundantly infiltrated by myeloid immune populations but scarcely by T lymphocytes, as determined by single-nucleus RNA sequencing and high-dimensional leukocyte profiling. Such tumors failed to respond to programmed cell death-1 (PD-1) blockade, but reduced their growth on treatment with ER antagonists, as well as with anthracycline-based chemotherapy, which was not influenced by T-cell depletion. Moreover, B6BC-derived tumors reduced their growth on CD11b blockade, indicating tumor sustainment by myeloid cells. The immune environment and treatment responses recapitulated by B6BC-derived tumors diverged from those of ER+ TS/A cell-derived tumors in BALB/C mice, and of ER– E0771 cell-derived and MPA/DMBA-induced tumors in C57BL/6 mice.Conclusions B6BC is the first transplantable HR+ BC cell line derived from C57BL/6 mice and B6BC-derived tumors recapitulate the complex tumor microenvironment of locally advanced HR+ BC naturally resistant to PD-1 immunotherapy.
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- 2023
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10. Pharmacological inhibitors of anaplastic lymphoma kinase (ALK) induce immunogenic cell death through on-target effects
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Adriana Petrazzuolo, Maria Perez-Lanzon, Isabelle Martins, Peng Liu, Oliver Kepp, Véronique Minard-Colin, Maria Chiara Maiuri, and Guido Kroemer
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Cytology ,QH573-671 - Abstract
Abstract Immunogenic cell death (ICD) is clinically relevant because cytotoxicants that kill malignant cells via ICD elicit anticancer immune responses that prolong the effects of chemotherapies beyond treatment discontinuation. ICD is characterized by a series of stereotyped changes that increase the immunogenicity of dying cells: exposure of calreticulin on the cell surface, release of ATP and high mobility group box 1 protein, as well as a type I interferon response. Here, we examined the possibility that inhibition of an oncogenic kinase, anaplastic lymphoma kinase (ALK), might trigger ICD in anaplastic large cell lymphoma (ALCL) in which ALK is activated due to a chromosomal translocation. Multiple lines of evidence plead in favor of specific ICD-inducing effects of crizotinib and ceritinib in ALK-dependent ALCL: (i) they induce ICD stigmata at pharmacologically relevant, low concentrations; (ii) can be mimicked in their ICD-inducing effects by ALK knockdown; (iii) lose their effects in the context of resistance-conferring ALK mutants; (iv) ICD-inducing effects are mimicked by inhibition of the signal transduction pathways operating downstream of ALK. When ceritinib-treated murine ALK-expressing ALCL cells were inoculated into the left flank of immunocompetent syngeneic mice, they induced an immune response that slowed down the growth of live ALCL cells implanted in the right flank. Although ceritinib induced a transient shrinkage of tumors in lymphoma-bearing mice, irrespective of their immunocompetence, relapses occurred more frequently in the context of immunodeficiency, reducing the effects of ceritinib on survival by approximately 50%. Complete cure only occurred in immunocompetent mice and conferred protection to rechallenge with the same ALK-expressing lymphoma but not with another unrelated lymphoma. Moreover, immunotherapy with PD-1 blockade tended to increase cure rates. Altogether, these results support the contention that specific ALK inhibition stimulates the immune system by inducing ICD in ALK-positive ALCL.
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- 2021
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11. Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer
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Aitziber Buqué, Norma Bloy, Maria Perez-Lanzón, Kristina Iribarren, Juliette Humeau, Jonathan G. Pol, Sarah Levesque, Laura Mondragon, Takahiro Yamazaki, Ai Sato, Fernando Aranda, Sylvère Durand, Alexandre Boissonnas, Jitka Fucikova, Laura Senovilla, David Enot, Michal Hensler, Margerie Kremer, Gautier Stoll, Yang Hu, Chiara Massa, Silvia C. Formenti, Barbara Seliger, Olivier Elemento, Radek Spisek, Fabrice André, Laurence Zitvogel, Suzette Delaloge, Guido Kroemer, and Lorenzo Galluzzi
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Science - Abstract
Current preclinical models to investigate human HR + breast cancer progression and response to immunotherapy in vivo are limited. Here, the authors demonstrate that mammary tumours driven by a synthetic progestin combined with an oral carcinogen recapitulate several immunobiological features of human HR + breast cancers.
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- 2020
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12. Crizotinib and ceritinib trigger immunogenic cell death via on-target effects
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Adriana Petrazzuolo, Maria Perez-Lanzon, Peng Liu, M. Chiara Maiuri, and Guido Kroemer
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alk inhibitors ,immunogenicity ,anaplastic large cell lymphoma ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Immunogenic cell death (ICD) has initially been discovered in the context of chemotherapy. High-dose crizotinib also stimulates ICD, as we described for non-small cell lung cancer lacking activating chromosomal aberrations of ALK or ROS1, the usual targets of crizotinib, indicating that crizotinib may act through off-target effects. However, we found that low-dose of ALK inhibitors, crizotinib and ceritinib, may stimulate ICD in anaplastic large cell lymphoma, in which ALK is activated due to a chromosomal translocation, suggesting on target ICD-promoting effects.
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- 2021
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13. Lurbinectedin synergizes with immune checkpoint blockade to generate anticancer immunity
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Wei Xie, Sabrina Forveille, Kristina Iribarren, Allan Sauvat, Laura Senovilla, Yan Wang, Juliette Humeau, Maria Perez-Lanzon, Heng Zhou, Juan F. Martínez-Leal, Guido Kroemer, and Oliver Kepp
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anticancer immunity ,immunogenic cell death ,checkpoint blockade ,tumor clearance ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Systemic treatment with the active transcription inhibitor lurbinectedin aims at inducing tumor cell death in hyperproliferative neoplasms. Here we show that cell death induced by lurbinectedin reinstates and enhances systemic anticancer immune responses. Lurbinectedin treatment showed traits of immunogenic cell death, including the exposure of calreticulin, the release of ATP, the exodus of high mobility group box 1 (HMGB1) and type 1 interferon responses in vitro. Lurbinectedin treated cells induced antitumor immunity when injected into immunocompetent animals and treatment of transplanted fibrosarcomas reduced tumor growth in immunocompetent yet not in immunodeficient hosts. Anticancer effects resulting from lurbinectedin treatment were boosted in combination with PD-1 and CTLA-4 double immune checkpoint blockade (ICB), and lurbinectedin combined with double ICB exhibited strong antineoplastic effects. Cured animals exhibited long term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors underlining the potency of combination therapy with lurbinectedin.
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- 2019
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14. Failure of immunosurveillance accelerates aging
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Maria Perez-Lanzon, Laurence Zitvogel, and Guido Kroemer
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age-related disease ,cytotoxic t cells ,nk cells ,immunosenescence ,senescence ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Immunosurveillance is generally conceived as a mechanism through which the immune system detects and eliminates (pre-)malignant cells, thus reducing the risk of developing cancer. A recent paper by Ovadya et al. demonstrates that knockout of the gene coding for perforin-1 causes accelerated accumulation of senescent cells in multiple mouse organs, thereby speeding up the aging process. These results suggest that immunosurveillance plays a much broader role in maintaining organismal health than it had been suspected.
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- 2019
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15. Publisher Correction: Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer
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Aitziber Buqué, Norma Bloy, Maria Perez-Lanzón, Kristina Iribarren, Juliette Humeau, Jonathan G. Pol, Sarah Levesque, Laura Mondragon, Takahiro Yamazaki, Ai Sato, Fernando Aranda, Sylvère Durand, Alexandre Boissonnas, Jitka Fucikova, Laura Senovilla, David Enot, Michal Hensler, Margerie Kremer, Gautier Stoll, Yang Hu, Chiara Massa, Silvia C. Formenti, Barbara Seliger, Olivier Elemento, Radek Spisek, Fabrice André, Laurence Zitvogel, Suzette Delaloge, Guido Kroemer, and Lorenzo Galluzzi
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Science - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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