CD4⁺ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors.

ABSTRACT: CD4⁺ T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8⁺ cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4⁺ T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4⁺ T cells in humans. Activated CD4⁺ T cells produce IFNβ via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses. In cooperation with CD40 ligand (L), IFNβ also optimizes the costimulatory

SUBMITTER: Lei X 

PROVIDER: S-EPMC10978876 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature