Functionally heterogeneous intratumoral CD4⁺CD8⁺ double-positive T cells can give rise to single-positive T cells.

ABSTRACT: Conventional single-positive (SP) CD4⁺ and CD8⁺ T cells recognize tumor antigens and help mediate clinical responses with cancer immunotherapy. Double-positive CD4⁺CD8⁺ (DP) T cells have also been described in human cancers, but their role in the tumor microenvironment remains unclear. By generating a multiomic single cell atlas of DP and SP T cells, we find that DP T cells possess phenotypic heterogeneity similar to SP T cells that includes multiple clonally expanded populations of cytotoxic DP T cells in human renal cell carcinoma (RCC). These intratumoral DP T cells can mediate both MHC class I- and class II-dependent killing of autologous tumor cells. In addition, transcriptional profiling of DP TCR-bearing T cells revealed a gene signature e

SUBMITTER: Li T 

PROVIDER: S-EPMC12849695 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature