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CD103(+)CD8(+) T(RM) Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17

Accumulation of CD103(+)CD8(+) resident memory T (T(RM)) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of T(RM) to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multipl...

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Detalles Bibliográficos
Autores principales: Corgnac, Stéphanie, Malenica, Ines, Mezquita, Laura, Auclin, Edouard, Voilin, Elodie, Kacher, Jamila, Halse, Heloise, Grynszpan, Laetitia, Signolle, Nicolas, Dayris, Thibault, Leclerc, Marine, Droin, Nathalie, de Montpréville, Vincent, Mercier, Olaf, Validire, Pierre, Scoazec, Jean-Yves, Massard, Christophe, Chouaib, Salem, Planchard, David, Adam, Julien, Besse, Benjamin, Mami-Chouaib, Fathia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659589/
https://www.ncbi.nlm.nih.gov/pubmed/33205076
http://dx.doi.org/10.1016/j.xcrm.2020.100127
Descripción
Sumario:Accumulation of CD103(+)CD8(+) resident memory T (T(RM)) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of T(RM) 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 T(RM), 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(+) T(RM) are associated with better outcomes in anti-PD-(L)1-treated patients.