Identification and regulation of circulating tumor-TCR-matched cytotoxic CD4+ lymphocytes by KLRG1 in bladder cancer.

ABSTRACT: While cytotoxic CD4+ tumor-infiltrating lymphocytes have anticancer activity in patients, whether these can be noninvasively monitored and how these are regulated remains obscure. By matching single cells with T cell receptors (TCRs) in tumor and blood of patients with bladder cancer, we identified distinct pools of tumor-matching cytotoxic CD4+ T cells in the periphery directly reflecting the predominant antigenic specificities of intratumoral CD4+ tumor-infiltrating lymphocytes. On one hand, the granzyme B-expressing (GZMB-expressing) cytotoxic CD4+ subset proliferated in blood in response to PD-1 blockade but was separately regulated by the killer cell lectin-like receptor G1 (KLRG1), which inhibited their killing by interacting with E-cadherin. Conversely, a clonally related, GZMK-expr

SUBMITTER: Kwek SS 

PROVIDER: S-EPMC12220972 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature