Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade.

ABSTRACT: The circadian clock is a critical regulator of immunity, and this circadian control of immune modulation has an essential function in host defense and tumor immunosurveillance. Here we use a single-cell RNA sequencing approach and a genetic model of colorectal cancer to identify clock-dependent changes to the immune landscape that control the abundance of immunosuppressive cells and consequent suppression of cytotoxic CD8⁺ T cells. Of these immunosuppressive cell types, PD-L1-expressing myeloid-derived suppressor cells (MDSCs) peak in abundance in a rhythmic manner. Disruption of the epithelial cell clock regulates the secretion of cytokines that promote heightened inflammation, recruitment of neutrophils and the subsequent development of MDSCs. We also show that time-of-day ant

SUBMITTER: Fortin BM 

PROVIDER: S-EPMC11374317 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature