PD-1 blockade-unresponsive human tumor-infiltrating CD8⁺ T cells are marked by loss of CD28 expression and rescued by IL-15.

ABSTRACT: Blockade of programmed death-1 (PD-1) reinvigorates exhausted CD8⁺ T cells, resulting in tumor regression in cancer patients. Recently, reinvigoration of exhausted CD8⁺ T cells following PD-1 blockade was shown to be CD28-dependent in mouse models. Herein, we examined the role of CD28 in anti-PD-1 antibody-induced human T cell reinvigoration using tumor-infiltrating CD8⁺ T cells (CD8⁺ TILs) obtained from non-small-cell lung cancer patients. Single-cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8⁺ TILs. Furthermore, we found that human CD28⁺CD8⁺ but not CD28^-CD8⁺ TILs responded to PD-1 blockade irrespective of B7/CD28 blockade, indicating that CD28 c

SUBMITTER: Kim KH 

PROVIDER: S-EPMC8027446 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature