HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8⁺ T-cell infiltration into tumors.

ABSTRACT: The lack of tumor infiltration by CD8⁺ T cells is associated with poor patient response to anti-PD-1 therapy. Understanding how tumor infiltration is regulated is key to improving treatment efficacy. Here, we report that phosphorylation of HRS, a pivotal component of the ESCRT complex involved in exosome biogenesis, restricts tumor infiltration of cytolytic CD8⁺ T cells. Following ERK-mediated phosphorylation, HRS interacts with and mediates the selective loading of PD-L1 to exosomes, which inhibits the migration of CD8⁺ T cells into tumors. In tissue samples from patients with melanoma, CD8⁺ T cells are excluded from the regions where tumor cells contain high levels of phosphorylated HRS. In murine tumor models, overexpression of phosphorylated

SUBMITTER: Guan L 

PROVIDER: S-EPMC9283393 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature