CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17
| Autor: | Julien Adam, Heloise Halse, Pierre Validire, David Planchard, Jamila Kacher, Marine Leclerc, Stéphanie Corgnac, Olaf Mercier, Christophe Massard, Laura Mezquita, Fathia Mami-Chouaib, Nathalie Droin, Ines Malenica, Salem Chouaib, Edouard Auclin, Benjamin Besse, Vincent Thomas de Montpréville, Jean-Yves Scoazec, Nicolas Signolle, Laetitia Grynszpan, Elodie Voilin, Thibault Dayris |
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| Přispěvatelé: | Immunologie intégrative des tumeurs (UMR 1186), 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), 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), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Hôpital Marie-Lannelongue, Institut Mutualiste de Montsouris (IMM), Département de biologie et pathologie médicales [Gustave Roussy], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Département de médecine oncologique [Gustave Roussy], CCSD, Accord Elsevier, Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique moléculaire de la transformation hématopoïétique (Dynamo) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cytotoxicity
Immunologic Lung Neoplasms medicine.medical_treatment [SDV]Life Sciences [q-bio] Programmed Cell Death 1 Receptor CD8-Positive T-Lymphocytes CD103 integrin Lymphocyte Activation B7-H1 Antigen CD49a anti-PD-1 immunotherapy 0302 clinical medicine Antineoplastic Agents Immunological Carcinoma Non-Small-Cell Lung Tumor Microenvironment Phosphorylation Cytotoxicity ComputingMilieux_MISCELLANEOUS lcsh:R5-920 0303 health sciences Chemistry Interleukin-17 hemic and immune systems Prognosis Aiolos 3. Good health [SDV] Life Sciences [q-bio] 030220 oncology & carcinogenesis tumor-infiltrating lymphocytes Immunotherapy lcsh:Medicine (General) Integrin alpha Chains Signal Transduction STAT3 Transcription Factor CD8 Antigens and T-bet transcription factors Tc17 chemical and pharmacologic phenomena General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Ikaros Transcription Factor Lymphocytes Tumor-Infiltrating Antigens CD medicine Humans Lymphocyte Count Lung cancer 030304 developmental biology Retrospective Studies ICB response biomarkers Tumor-infiltrating lymphocytes AhR medicine.disease Survival Analysis Immune checkpoint CD8 TRM cells Aiolos AhR and T-bet transcription factors TCR repertoire lung cancer Gene Expression Regulation Cancer cell CTL Cancer research Immunologic Memory CD8 |
| Zdroj: | Cell Reports Medicine Cell Reports Medicine, 2020, 1, pp.100127-. ⟨10.1016/j.xcrm.2020.100127⟩ Cell Reports Medicine, Cell Press, 2020, 1, pp.100127-. ⟨10.1016/j.xcrm.2020.100127⟩ Cell Reports Medicine, Vol 1, Iss 7, Pp 100127-(2020) |
| ISSN: | 2666-3791 |
| DOI: | 10.1016/j.xcrm.2020.100127⟩ |
| Popis: | Summary Accumulation of CD103+CD8+ resident memory T (TRM) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of TRM to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103+CD8+ lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes. The density of CD103+CD8+ cells increases during immunotherapy in most responder, but not in non-responder, patients. CD103+CD8+ cells co-express CD49a and CD69 and display a molecular profile characterized by the expression of PD-1 and CD39. CD103+CD8+ tumor TRM, but not CD103−CD8+ tumor-infiltrating counterparts, express Aiolos, phosphorylated STAT-3, and IL-17; demonstrate enhanced proliferation and cytotoxicity toward autologous cancer cells; and frequently display oligoclonal expansion of TCR-β clonotypes. These results explain why CD103+CD8+ TRM are associated with better outcomes in anti-PD-(L)1-treated patients. Graphical Abstract Highlights A high density of CD103+CD8+ cells in tumors correlates with response to anti-PD-(L)1 The density of CD103+CD8+ cells increases after anti-PD-1 in most responder patients CD103+CD8+ TRM cells are enriched with tumor-specific T cells A subset of CD103+CD8+ TRM cells display a Tc17 differentiation program Using retrospective cohorts of anti-PD-(L)1-treated NSCLC, Corgnac et al. show that the density of CD103+CD8+ cells in tumors is associated with better progression-free survival. CD103+CD8+ tumor-infiltrating lymphocytes are tumor-specific resident memory T cells (TRM) enriched with a subset displaying a unique Tc1/Tc17 differentiation program that differs from CD103−CD8+ T cells (non-TRM). |
| Databáze: | OpenAIRE |
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