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51. Targeting MICA/B with cytotoxic therapeutic antibodies leads to tumor control

Author

Bléry, Mathieu, primary, Mrabet-Kraiem, Manel, additional, Morel, Ariane, additional, Lhospice, Florence, additional, Bregeon, Delphine, additional, Bonnafous, Cécile, additional, Gauthier, Laurent, additional, Rossi, Benjamin, additional, Remark, Romain, additional, Cornen, Stéphanie, additional, Anceriz, Nadia, additional, Viaud, Nicolas, additional, Trichard, Sylvia, additional, Carpentier, Sabrina, additional, Joulin-Giet, Alix, additional, Grondin, Gwendoline, additional, Liptakova, Veronika, additional, Kim, Younghoon, additional, Daniel, Laurent, additional, Haffner, Aurélie, additional, Macagno, Nicolas, additional, Pouyet, Laurent, additional, Perrot, Ivan, additional, Paturel, Carine, additional, Morel, Yannis, additional, Steinle, Alexander, additional, Romagné, François, additional, Narni-Mancinelli, Emilie, additional, and Vivier, Eric, additional

Published
2021
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52. Anti–GM-CSF autoantibodies promote a “pre-diseased” state in Crohn’s Disease

Author

Mortha, Arthur, primary, Remark, Romain, additional, Del Valle, Diane Marie, additional, Chuang, Ling-Shiang, additional, Chai, Zhi, additional, Alves, Inês, additional, Azevedo, Catarina, additional, Gaifem, Joana, additional, Martin, Jerome, additional, Tuballes, Kevin, additional, Barcessat, Vanessa, additional, Tai, Siu Ling, additional, Huang, Hsin-Hui, additional, Laface, Ilaria, additional, Jerez, Yeray Arteaga, additional, Boschetti, Gilles, additional, Villaverde, Nicole, additional, Wang, Mona D., additional, Korie, Ujunwa M., additional, Murray, Joseph, additional, Choung, Rok-Seon, additional, Sato, Takahiro, additional, Laird, Renee M., additional, Plevy, Scot, additional, Rahman, Adeeb, additional, Torres, Joana, additional, Porter, Chad, additional, Riddle, Mark S., additional, Kenigsberg, Ephraim, additional, Pinho, Salomé S., additional, Cho, Judy H., additional, Merad, Miriam, additional, Colombel, Jean-Frederic, additional, and Gnjatic, Sacha, additional

Published
2021
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53. Presence of B Cells in Tertiary Lymphoid Structures Is Associated with a Protective Immunity in Patients with Lung Cancer

Author

Germain, Claire, Gnjatic, Sacha, Tamzalit, Fella, Knockaert, Samantha, Remark, Romain, Goc, Jérémy, Lepelley, Alice, Becht, Etienne, Katsahian, Sandrine, Bizouard, Geoffray, Validire, Pierre, Damotte, Diane, Alifano, Marco, Magdeleinat, Pierre, Cremer, Isabelle, Teillaud, Jean-Luc, Fridman, Wolf-Herman, Sautès-Fridman, Catherine, and Dieu-Nosjean, Marie-Caroline

Published
2014
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54. 483 Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis

Author

Demaria, Olivier, primary, Carvelli, Julien, additional, Benmansour, Nassima Chouaki, additional, Fares, Joanna, additional, Batista, Luciana, additional, Thibult, Marie-Laure, additional, Morel, Ariane, additional, Carpentier, Sabrina, additional, Remark, Romain, additional, Represa, Agnes, additional, Vely, Frederic, additional, Ebbo, Mikael, additional, Schleinitz, Nicolas, additional, Zerbib, Robert, additional, Morel, Yannis, additional, Vivier, Eric, additional, and Demaria, Olivier, additional

Published
2020
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55. CD3 and CD20 immune cell densities in primary tumors, lymph node metastasis, and recurrent disease samples of head and neck squamous cell carcinoma.

Author

Laban, Simon, primary, Remark, Romain, additional, Idel, Christian, additional, Ribbat-Idel, Julika, additional, Schröck, Andreas, additional, Ezić, Jasmin, additional, Döscher, Johannes, additional, Theodoraki, Marie-Nicole, additional, Krupar, Rosemarie, additional, Sikora, Andrew G., additional, Kristiansen, Glen, additional, Bootz, Friedrich, additional, Akturk, Guray, additional, Ettrich, Thomas Jens, additional, El-Osta, Hazem Edmond, additional, Schuler, Patrick J, additional, Brunner, Cornelia, additional, Hoffmann, Thomas K, additional, Perner, Sven, additional, and Gnjatic, Sacha, additional

Published
2020
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56. Additional file 1: of Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment

Author

Courau, Tristan, Bonnereau, Julie, Chicoteau, Justine, Bottois, Hugo, Remark, Romain, Miranda, Laura Assante, Toubert, Antoine, Blery, Mathieu, Aparicio, Thomas, Allez, Matthieu, and Bourhis, Lionel Le

Subjects
embryonic structures
Abstract

Figure S1. Tregs infiltration in HT29 spheroids. Percentages of Foxp3+CD25+ Tregs among CD4+ T cells analyzed in Fig. 1c and d. Figure S2. IFNg blockade decreases spheroid infiltration and destruction by immune cells. (A) Pictures and analyses of (B) spheroid volume, (C) tumor cell apoptosis, and (D) spheroid infiltration 48h after coculturing HT29 spheroids with CD19-CD14- PBMCs in the presence or not of anti-IFNg blocking antibodies. Figure S3. T cell subsets and NKG2D expression by CD8 T cells after MICA/B treatment. (A) CD4 and (B) CD8 T cells proportions as well as (C) NKG2D expression by CD8 T cells relative to experiments in Fig. 5f to k. Figure S4. T and NK cells proportions and CD137 expression by CD8 T cells after combination therapy. Proportions of (A) T and NK cells, of (B) CD4 and CD8 T cells subsets and (C) CD137 expression by CD8 T cells relative to Fig. 6g to h. Figure S5. Pictures of primary CRC tumors cultures. Pictures of (A) primary CRC tumor cultured in adherent culture flasks and (B) tumor-derived spheroids used in autologous cocultures. Figure S6. Primary CRC-derived spheroids contains significant amount of EpCAM+ tumor cells. (A) Picture of primary CRC-derived spheroids and (B) flow cytometry or (C) IF analyses of EpCAM+ staining in the spheroids. Table S1. Clinical characteristics of the patients used for autologous cocultures. Table 2. Tumor cells content of the spheroids and T and NK cells composition of the TILs used for autologous cocultures. Percentages of tumor cells (EpCAM+CD45-) in patients-derived spheroids and percentages of NK cells (CD3e-CD56+) and T cells (overall CD3+, CD4 T cells CD3+CD4+CD8-, CD8 T cells CD3+CD4-CD8+) in respective autologous TILs used for cocultures. (DOCX 24846 kb)

Published
2019
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57. Immune Profiling of Atherosclerotic Plaques Identifies Innate and Adaptive Dysregulations Associated with Ischemic Cerebrovascular Events

Author

Fernandez, Dawn M., primary, Rahman, Adeeb H., additional, Fernandez, Nicolas, additional, Chudnovskiy, Aleksey, additional, Amir, El-ad David, additional, Amadori, Letizia, additional, Khan, Nayaab S., additional, Wong, Christine, additional, Shamailova, Roza, additional, Hill, Christopher, additional, Wang, Zichen, additional, Remark, Romain, additional, Li, Jennifer R., additional, Pina, Christian, additional, Faries, Christopher, additional, Awad, Ahmed J., additional, Moss, Noah, additional, Bjorkegren, Johan L.M., additional, Kim-Schulze, Seunghee, additional, Gnjatic, Sacha, additional, Ma’ayan, Avi, additional, Mocco, J., additional, Faries, Peter, additional, Merad, Miriam, additional, and Giannarelli, Chiara, additional

Published
2019
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59. Abstract IA31: Measuring the emergence of non-self in tumors

Author

Luksza, Marta, primary, Solovyov, Alexander, additional, Vabret, Nicolas, additional, Balachandran, Vinod, additional, Riaz, Nadeem, additional, Makarov, Vladimir, additional, Hellmann, Matthew D., additional, Snyder, Alexandra, additional, Funt, Samuel, additional, Remark, Romain, additional, Merad, Miriam, additional, Gnjatic, Sacha, additional, Bajorin, Dean F., additional, Rosenberg, Jonathan, additional, Leach, Steven, additional, Levine, Arnold J., additional, Chan, Timothy A., additional, Bhardwaj, Nina, additional, Wolchock, Jedd, additional, and Greenbaum, Benjamin D., additional

Published
2019
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60. Identification of unique neoantigen qualities in long term pancreatic cancer survivors

Author

Balachandran, Vinod P., Łuksza, Marta, Zhao, Julia N., Makarov, Vladimir, Moral, John Alec, Remark, Romain, Herbst, Brian, Askan, Gokce, Bhanot, Umesh, Senbabaoglu, Yasin, Wells, Daniel K., Cary, Charles Ian Ormsby, Grbovic-Huezo, Olivera, Attiyeh, Marc, Medina, Benjamin, Zhang, Jennifer, Loo, Jennifer, Saglimbeni, Joseph, Abu-Akeel, Mohsen, Zappasodi, Roberta, Riaz, Nadeem, Smoragiewicz, Martin, Kelley, Z. Larkin, Basturk, Olca, Gönen, Mithat, Levine, Arnold J., Allen, Peter J., Fearon, Douglas T., Merad, Miriam, Gnjatic, Sacha, Iacobuzio-Donahue, Christine A., Wolchok, Jedd D., DeMatteo, Ronald P., Chan, Timothy A., Greenbaum, Benjamin D., Merghoub, Taha, and Leach, Steven D.

Subjects
Pancreatic Neoplasms, Humans, Survivors, Article, Algorithms
Published
2017

61. Abstract 2714: Combination of monalizumab and durvalumab as a potent immunotherapy treatment for solid human cancers

Author

Soulas, Caroline, primary, Remark, Romain, additional, Brezar, Vedran, additional, Lopez, Julie, additional, Bonnet, Elodie, additional, Caraguel, Flavien, additional, Lalanne, Ana, additional, Hoffmann, Caroline, additional, Denis, Caroline, additional, Arnoux, Thomas, additional, Caillet, Clarisse, additional, Dujardin, Arnaud, additional, Habif, Guillaume, additional, Lantz, Olivier, additional, Bonnafous, Cécile, additional, Vivier, Eric, additional, and Andre, Pascale, additional

Published
2018
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62. Abstract 2718: Preclinical development of humanized CD39 and CD73 blocking antibodies targeting the ATP/adenosine immune checkpoint pathway for cancer immunotherapy

Author

Perrot, Ivan, primary, Paoli, Marc Giraudon, additional, Augier, Séverine, additional, Blemont, Marilyne Royannez, additional, Gaudin, Marion, additional, Bosco, Frédéric, additional, Courtois, Rachel, additional, Delahaye, Stephane, additional, Jecko, Diana, additional, Gourdin, Nicolas, additional, Agu, Maryline Salin, additional, Perrier, Cyril, additional, Ricaut, Paul, additional, Docquier, Aurélie, additional, Chanteux, Stéphanie, additional, Rossi, Benjamin, additional, Représa, Agnès, additional, Denis, Caroline, additional, Remark, Romain, additional, Bonnafous, Cécile, additional, Gauthier, Laurent, additional, Morel, Ariane, additional, Bonnefoy, Nathalie, additional, Bastid, Jérémy, additional, Morel, Yannis, additional, and Paturel, Carine, additional

Published
2018
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63. Abstract 1690: NKG2A immune checkpoint blockade potentiates cetuximab induced ADCC in head and neck cancer preclinical model

Author

Soulas, Caroline, primary, Lalanne, Ana, additional, Bonnafous, Cécile, additional, Hoffman, Caroline, additional, Bonnet, Elodie, additional, Dujardin, Arnaud, additional, Breso, Violette, additional, Bléry, Mathieu, additional, Lantz, Olivier, additional, Remark, Romain, additional, Vivier, Eric, additional, and Andre, Pascale, additional

Published
2018
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64. Die Kombination aus dichtem T-Zell-Infiltrat und PD-L1 Expression identifiziert Kopf-Hals-Tumor Patienten mit besonders guter Prognose.

Author

Laban, Simon, Remark, Romain, Idel, Christian, Ribbat-Idel, Julika, Krupar, Rosemarie, Schröck, Andreas, Klümper, Niklas, Döscher, Johannes, Sikora, Andrew G., Abou Kors, Tsima, von Witzleben, Adrian, Vahl, Julius, Grages, Ayla, Sonntag, Michael, Brunner, Cornelia, Hoffmann, Thomas, Perner, Sven, and Gnjatic, Sacha

Published
2024
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65. RAF/MEK/extracellular signal–related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions

Author

Hogstad, Brandon, primary, Berres, Marie-Luise, additional, Chakraborty, Rikhia, additional, Tang, Jun, additional, Bigenwald, Camille, additional, Serasinghe, Madhavika, additional, Lim, Karen Phaik Har, additional, Lin, Howard, additional, Man, Tsz-Kwong, additional, Remark, Romain, additional, Baxter, Samantha, additional, Kana, Veronika, additional, Jordan, Stefan, additional, Karoulia, Zoi, additional, Kwan, Wing-hong, additional, Leboeuf, Marylene, additional, Brandt, Elisa, additional, Salmon, Helene, additional, McClain, Kenneth, additional, Poulikakos, Poulikos, additional, Chipuk, Jerry, additional, Mulder, Willem J.M., additional, Allen, Carl E., additional, and Merad, Miriam, additional

Published
2017
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66. Abstract 334: PTEN-L regulates epithelial growth and macrophage function

Author

Wolfe, Andrew L., primary, Hopkins, Benjamin D., additional, Riquelme, Sebastián A., additional, Kitur, Kipyegon, additional, Ozturk, Sait, additional, Kang, Kyeongah, additional, Remark, Romain, additional, Rahman, Adeeb, additional, Lin, Chyuan-Sheng, additional, Merad, Miriam, additional, Szabolcs, Matthias, additional, Chen, Shu-Hsia, additional, Prince, Alice, additional, and Parsons, Ramon, additional

Published
2017
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67. Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging

Author

Hectors, Stefanie J., primary, Wagner, Mathilde, additional, Bane, Octavia, additional, Besa, Cecilia, additional, Lewis, Sara, additional, Remark, Romain, additional, Chen, Nelson, additional, Fiel, M. Isabel, additional, Zhu, Hongfa, additional, Gnjatic, Sacha, additional, Merad, Miriam, additional, Hoshida, Yujin, additional, and Taouli, Bachir, additional

Published
2017
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68. Abstract 439: High Dimensional Single-Cell Immune Contexture of Human Atherosclerotic Plaques and Blood

Author

Rahman, Adeeb, primary, Chudnovskiy, Aleksey, additional, Amir, El-ad David, additional, Kim-Schulze, Seunghee, additional, Li, Jennifer R, additional, Pina, Christian, additional, Moss, Noah, additional, Remark, Romain, additional, Gnjatic, Sacha, additional, Faries, Peter, additional, Merad, Miriam, additional, and Giannarelli, Chiara, additional

Published
2017
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69. MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy

Author

Laban, Simon, primary, Giebel, Gregor, additional, Klümper, Niklas, additional, Schröck, Andreas, additional, Doescher, Johannes, additional, Spagnoli, Giulio, additional, Thierauf, Julia, additional, Theodoraki, Marie-Nicole, additional, Remark, Romain, additional, Gnjatic, Sacha, additional, Krupar, Rosemarie, additional, Sikora, Andrew G., additional, Litjens, Geert, additional, Grabe, Niels, additional, Kristiansen, Glen, additional, Bootz, Friedrich, additional, Schuler, Patrick J., additional, Brunner, Cornelia, additional, Brägelmann, Johannes, additional, Hoffmann, Thomas K., additional, and Perner, Sven, additional

Published
2017
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70. Immune contexture and histological response after neoadjuvant chemotherapy predict clinical outcome of lung cancer patients

Author

Remark, Romain, primary, Lupo, Audrey, additional, Alifano, Marco, additional, Biton, Jerome, additional, Ouakrim, Hanane, additional, Stefani, Alessandro, additional, Cremer, Isabelle, additional, Goc, Jeremy, additional, Régnard, Jean-Francois, additional, Dieu-Nosjean, Marie-Caroline, additional, and Damotte, Diane, additional

Published
2016
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73. Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome

Author

Chudnovskiy, Aleksey, primary, Mortha, Arthur, additional, Kana, Veronika, additional, Kennard, Andrea, additional, Ramirez, Juan David, additional, Rahman, Adeeb, additional, Remark, Romain, additional, Mogno, Ilaria, additional, Ng, Ruby, additional, Gnjatic, Sasha, additional, Amir, El-ad David, additional, Solovyov, Alexander, additional, Greenbaum, Benjamin, additional, Clemente, Jose, additional, Faith, Jeremiah, additional, Belkaid, Yasmine, additional, Grigg, Michael E., additional, and Merad, Miriam, additional

Published
2016
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75. Calreticulin Expression in Human Non–Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis

Author

Fucikova, Jitka, primary, Becht, Etienne, additional, Iribarren, Kristina, additional, Goc, Jeremy, additional, Remark, Romain, additional, Damotte, Diane, additional, Alifano, Marco, additional, Devi, Priyanka, additional, Biton, Jerome, additional, Germain, Claire, additional, Lupo, Audrey, additional, Fridman, Wolf Herve, additional, Dieu-Nosjean, Marie-Caroline, additional, Kroemer, Guido, additional, Sautès-Fridman, Catherine, additional, and Cremer, Isabelle, additional

Published
2016
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77. A multimodal imaging workflow to visualize metal mixtures in the human placenta and explore colocalization with biological response markers

Author

Niedzwiecki, Megan M., primary, Austin, Christine, additional, Remark, Romain, additional, Merad, Miriam, additional, Gnjatic, Sacha, additional, Estrada-Gutierrez, Guadalupe, additional, Espejel-Nuñez, Aurora, additional, Borboa-Olivares, Hector, additional, Guzman-Huerta, Mario, additional, Wright, Rosalind J., additional, Wright, Robert O., additional, and Arora, Manish, additional

Published
2016
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79. Dendritic Cells in Tumor-Associated Tertiary Lymphoid Structures Signal a Th1 Cytotoxic Immune Contexture and License the Positive Prognostic Value of Infiltrating CD8+ T Cells

Author

Goc, Jérémy, primary, Germain, Claire, additional, Vo-Bourgais, Thi Kim Duy, additional, Lupo, Audrey, additional, Klein, Christophe, additional, Knockaert, Samantha, additional, de Chaisemartin, Luc, additional, Ouakrim, Hanane, additional, Becht, Etienne, additional, Alifano, Marco, additional, Validire, Pierre, additional, Remark, Romain, additional, Hammond, Scott A., additional, Cremer, Isabelle, additional, Damotte, Diane, additional, Fridman, Wolf-Herman, additional, Sautès-Fridman, Catherine, additional, and Dieu-Nosjean, Marie-Caroline, additional

Published
2014
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80. Characteristics and Clinical Impacts of the Immune Environments in Colorectal and Renal Cell Carcinoma Lung Metastases: Influence of Tumor Origin

Author

Remark, Romain, primary, Alifano, Marco, additional, Cremer, Isabelle, additional, Lupo, Audrey, additional, Dieu-Nosjean, Marie-Caroline, additional, Riquet, Marc, additional, Crozet, Lucile, additional, Ouakrim, Hanane, additional, Goc, Jeremy, additional, Cazes, Aurélie, additional, Fléjou, Jean-François, additional, Gibault, Laure, additional, Verkarre, Virginie, additional, Régnard, Jean-François, additional, Pagès, Olivier-Nicolas, additional, Oudard, Stéphane, additional, Mlecnik, Bernhard, additional, Sautès-Fridman, Catherine, additional, Fridman, Wolf-Herman, additional, and Damotte, Diane, additional

Published
2013
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81. Abstract LB-498: Density of tertiary lymphoid structures is associated with activated and effector-memory T lymphocyte infiltration in human lung tumor

Author

Goc, Jeremy, primary, de Chaisemartin, Luc, additional, Damotte, Diane, additional, Validire, Pierre, additional, Lupo, Audrey, additional, Devevre, Estelle, additional, Remark, Romain, additional, Magdeleinat, Pierre, additional, Alifano, Marco, additional, Cremer, Isabelle, additional, Fridman, Wolf-Herman, additional, Sautès-Fridman, Catherine, additional, and Dieu-Nosjean, Marie-Caroline, additional

Published
2012
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82. Abstract LB-497: Primary tumor localization determines the metastatic immune profile

Author

Remark, Romain, primary, Crozet, Lucile, additional, Lupo, Audrey, additional, Alifano, Marco, additional, Riquet, Marc, additional, Cremer, Isabelle, additional, Dieu-Nosjean, Marie-Caroline, additional, Goc, Jeremy, additional, Mlecnik, Bernhard, additional, Cazes, Aurelie, additional, Fléjou, Jean-François, additional, Gibault, Laure, additional, Verkarre, Virginie, additional, Oudard, Stéphane, additional, Pagès, Olivier, additional, Régnard, Jean-François, additional, Sautès-Fridman, Catherine, additional, Fridman, Wolf-Herman, additional, and Damotte, Diane, additional

Published
2012
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83. RAF/MEK/extracellular signal–related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions

Author

Hogstad, Brandon, Berres, Marie-Luise, Chakraborty, Rikhia, Tang, Jun, Bigenwald, Camille, Serasinghe, Madhavika, Lim, Karen Phaik Har, Lin, Howard, Man, Tsz-Kwong, Remark, Romain, Baxter, Samantha, Kana, Veronika, Jordan, Stefan, Karoulia, Zoi, Kwan, Wing-hong, Leboeuf, Marylene, Brandt, Elisa, Salmon, Helene, McClain, Kenneth, Poulikakos, Poulikos, Chipuk, Jerry, Mulder, Willem J.M., Allen, Carl E., and Merad, Miriam

Abstract

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207+ dendritic cells (DCs) with constitutively activated mitogen-activated protein kinase (MAPK) pathway signaling. Approximately 60% of LCH patients harbor somatic BRAFV600E mutations localizing to CD207+ DCs within lesions. However, the mechanisms driving BRAFV600E+ LCH cell accumulation in lesions remain unknown. Here we show that sustained extracellular signal–related kinase activity induced by BRAFV600E inhibits C-C motif chemokine receptor 7 (CCR7)–mediated DC migration, trapping DCs in tissue lesions. Additionally, BRAFV600E increases expression of BCL2-like protein 1 (BCL2L1) in DCs, resulting in resistance to apoptosis. Pharmacological MAPK inhibition restores migration and apoptosis potential in a mouse LCH model, as well as in primary human LCH cells. We also demonstrate that MEK inhibitor-loaded nanoparticles have the capacity to concentrate drug delivery to phagocytic cells, significantly reducing off-target toxicity. Collectively, our results indicate that MAPK tightly suppresses DC migration and augments DC survival, rendering DCs in LCH lesions trapped and resistant to cell death.

Published
2018
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84. Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas.

Author

Moll, Ellen, Fu, Yichun, Qian, Yingzhi, Perkins, Sara, Wieder, Shira, Gnjatic, Sacha, Remark, Romain, Bernardo, Sebastian, Moskalenko, Marina, Yao, Jonathan, Ferringer, Tammie, Chang, Rui, Chipuk, Jerry, Horst, Basil, Birge, Miriam, Phelps, Robert, and Saenger, Yvonne

Subjects
MELANOMA, TUMOR markers, TUMOR immunology, IMMUNOHISTOCHEMISTRY, CANCER relapse, CANCER patients
Abstract

Introduction: Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors. Methods: Sixty-two stage II-III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers. Results: We found, using Cox regression models, that the presence of TILs was associated with improved OS ( p = 0.034) and RFS ( p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma ( p = 0.632, 0.416). CD2 expression also was correlated with improved OS ( p = 0.021) and RFS ( p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma ( p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count. Conclusion: Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations. [ABSTRACT FROM AUTHOR]

Published
2015
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85. Dendritic Cells in Tumor-Associated Tertiary Lymphoid Structures Signal a Th1 Cytotoxic Immune Contexture and License the Positive Prognostic Value of Infiltrating CD8+ T Cells.

Author

Goc, Járámy, Germain, Claire, Vo-Bourgais, Thi Kim Duy, Lupo, Audrey, Klein, Christophe, Knockaert, Samantha, de Chaisemartin, Luc, Ouakrim, Hanane, Becht, Etienne, Alifano, Marco, Validire, Pierre, Remark, Romain, Hammond, Scott A., Cremer, Isabelle, Damotte, Diane, Fridman, Wolf-Herman, Sautás-Fridman, Catherine, and Dieu-Nosjean, Marie-Caroline

Subjects
*LYMPHATICS, *LUNG tumors, *IMMUNE response, *DENDRITIC cells, *T cells, *GENE expression, *CELL-mediated cytotoxicity, *TH1 cells
Abstract

Tumor-infiltrating T cells, particularly CD45RO+CD8+ memory T cells, confer a positive prognostic value in human cancers. However, the mechanisms that promote a protective T-cell response in the tumor microenvironment remain unclear. In chronic inflammatory settings such as the tumor microenvironment, lymphoid neogenesis can occur to create local lymph node-like structures known as tertiary lymphoid structures (TLS). These structures can exacerbate a local immune response, such that TLS formation in tumors may help promote an efficacious immune contexture. However, the role of TLS in tumors has yet to be investigated carefully. In lung tumors, mature dendritic cells (DC) present in tumor-associated TLS can provide a specificmarker of these structures. In this study, we evaluated the influence of TLS on the characteristics of the immune infiltrate in cohorts of prospective and retrospective human primary lung tumors (n=458). We found that a high density of mature DC correlated closely to a strong infiltration of T cells that are predominantly of the effector-memory phenotype. Moreover, mature DC density correlated with expression of genes related to T-cell activation, T-helper 1 (Th1) phenotype, and cytotoxic orientation. Lastly, a high density of TLS-associated DC correlated with long-term survival, which also allowed a distinction of patients with high CD8+ T-cell infiltration but a high risk of death. Taken together, our results show how tumors infiltrated by TLS-associated mature DC generate a specific immune contexture characterized by a strong Th1 and cytotoxic orientation that confers the lowest risk of death. Furthermore, our findings highlight the pivotal function of TLS in shaping the immune character of the tumor microenvironment, in promoting a protective immune response mediated by T cells against cancer [ABSTRACT FROM AUTHOR]

Published
2014
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86. Multiplexed Immunohistochemical Consecutive Staining on Single Slide (MICSSS): Multiplexed Chromogenic IHC Assay for High-Dimensional Tissue Analysis.

Author

Akturk G, Sweeney R, Remark R, Merad M, and Gnjatic S

Subjects
Chromogenic Compounds chemistry, Humans, Immunohistochemistry, Machine Learning, Paraffin Embedding, Tissue Fixation, Tumor Microenvironment, Biomarkers, Tumor metabolism, Neoplasms metabolism
Abstract

Disease states and cellular compartments can display a remarkable amount of heterogeneity, and truly appreciating this heterogeneity requires the ability to detect and probe each subpopulation present. A myriad of recent single-cell assays has allowed for in-depth analysis of these diverse cellular populations; however, fully understanding the interplay between each cell type requires knowledge not only of their mere presence but also of their spatial organization and their relation one to the other. Immunohistochemistry allows for the visualization of cells and tissue; however, standard techniques only allow for the use of very few probes on a single specimen, not allowing for in-depth analysis of complex cellular heterogeneity. A number of multiplex imaging techniques, such as immunofluorescence and multiplex immunohistochemistry, have been proposed to allow probing more cellular markers at once; however, many of these techniques still have their limitations. The use of fluorescent markers has an inherent limitation to the number of probes that can be simultaneously used due to spectral overlap. Moreover, other proposed multiplex IHC methods are time-consuming and require expensive reagents. Still, many of the methods rely on frozen tissue, which deviates from standards in human pathological evaluation. Here, we describe a multiplex IHC technique, staining for consecutive markers on a single slide, which utilizes similar steps and similar reagents as standard IHC, thus making it possible for any lab with standard IHC capabilities to perform this useful procedure. This method has been validated and confirmed that consecutive markers can be stained without the risk of cross-reactivity between staining cycles. Furthermore, we have validated that this technique does not lead to decreased antigenicity of subsequent epitopes probed, nor does it lead to steric hindrance.

Published
2020
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