Tumor-specific but immunosuppressive CD39⁺CD8⁺ T cells exhibit double-faceted roles in clear cell renal cell carcinoma.

ABSTRACT: CD39⁺CD8⁺ T cells are known as tumor-antigen-specific cells among CD8⁺ tumor-infiltrating lymphocytes (TILs). However, CD39⁺CD8⁺ T cells also reportedly exhibit immunosuppressive activity in hypoxic tumor models. Here, we investigate CD39⁺CD8⁺ TILs in clear cell renal cell carcinoma (ccRCC), a Von Hippel-Lindau (VHL) mutation-associated hypoxic tumor. Single-cell analyses confirm that CD39⁺CD8⁺ cells are a terminally exhausted subset of tumor-specific CD8⁺ TILs. CD39⁺CD8⁺ T cell development is directly induced by cAMP and T cell receptor (TCR) signaling. Analysis of a renal cell carcinoma (RCC) cohort reveals that the proportion of CD39⁺CD8⁺

SUBMITTER: Lee YJ 

PROVIDER: S-EPMC12629791 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature