PD-1-induced T cell exhaustion is controlled by a Drp1-dependent mechanism.

ABSTRACT: Programmed cell death-1 (PD-1) signaling downregulates the T-cell response, promoting an exhausted state in tumor-infiltrating T cells, through mostly unveiled molecular mechanisms. Dynamin-related protein-1 (Drp1)-dependent mitochondrial fission plays a crucial role in sustaining T-cell motility, proliferation, survival, and glycolytic engagement. Interestingly, such processes are exactly those inhibited by PD-1 in tumor-infiltrating T cells. Here, we show that PD-1^pos CD8⁺ T cells infiltrating an MC38 (murine adenocarcinoma)-derived murine tumor mass have a downregulated Drp1 activity and more elongated mitochondria compared with PD-1^neg counterparts. Also, PD-1^pos lymphocytic elements infiltrating a human colon cancer rarely express active Drp

SUBMITTER: Simula L 

PROVIDER: S-EPMC8732338 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature