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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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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 |
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. |
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