Tumor immunogenicity dictates reliance on TCF1 in CD8⁺ T cells for response to immunotherapy.

ABSTRACT: Stem-like CD8⁺ T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1⁺CD8⁺ T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen-specific CD8⁺ T cells and ICB response in poorly immunogenic tumors that accumulate TOX⁺ dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors. Importantly, improving T cell priming by vaccination or by enhancing antigen presentation on tumors rescues the defective responses of TCF1-deficient CD8⁺ T cell

SUBMITTER: Escobar G 

PROVIDER: S-EPMC10529353 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature