CD103+CD8+ TRM Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17
oleh: Stéphanie Corgnac, Ines Malenica, Laura Mezquita, Edouard Auclin, Elodie Voilin, Jamila Kacher, Heloise Halse, Laetitia Grynszpan, Nicolas Signolle, Thibault Dayris, Marine Leclerc, Nathalie Droin, Vincent de Montpréville, Olaf Mercier, Pierre Validire, Jean-Yves Scoazec, Christophe Massard, Salem Chouaib, David Planchard, Julien Adam, Benjamin Besse, Fathia Mami-Chouaib
| Format: | Article |
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| Diterbitkan: | Elsevier 2020-10-01 |
Deskripsi
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.