Deciphering immune predictors of immunotherapy response: A multiomics approach at the pan-cancer level.

ABSTRACT: Immune checkpoint blockade (ICB) therapy has transformed cancer treatment, yet many patients fail to respond. Employing single-cell multiomics, we unveil T cell dynamics influencing ICB response across 480 pan-cancer and 27 normal tissue samples. We identify four immunotherapy response-associated T cells (IRATs) linked to responsiveness or resistance and analyze their pseudotemporal patterns, regulatory mechanisms, and T cell receptor clonal expansion profiles specific to each response. Notably, transforming growth factor β1 (TGF-β1)+ CD4⁺ and Temra CD8⁺ T cells negatively correlate with therapy response, in stark contrast to the positive response associated with CXCL13+ CD4⁺ and CD8⁺ T cells. Validation with a cohort of 23 colorectal cancer (CRC

SUBMITTER: Li X 

PROVIDER: S-EPMC12047473 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature