A Burned-Out CD8⁺ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy.

ABSTRACT: Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non-small cell lung cancer (NSCLC). We identified a burned-out CD8⁺ TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFNγ and were the most apoptotic CD8⁺ TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B

SUBMITTER: Sanmamed MF 

PROVIDER: S-EPMC9421941 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature