Targeting metabotropic glutamate receptor 4 for cancer immunotherapy.

ABSTRACT: In this study, we report a novel role of metabotropic glutamate receptor 4 (GRM4) in suppressing antitumor immunity. We revealed in three murine syngeneic tumor models (B16, MC38, and 3LL) that either genetic knockout (Grm4^−/−) or pharmacological inhibition led to significant delay in tumor growth. Mechanistically, perturbation of GRM4 resulted in a strong antitumor immunity by promoting natural killer (NK), CD4⁺, and CD8⁺ T cells toward an activated, proliferative, and functional phenotype. Single-cell RNA sequencing and T cell receptor profiling further defined the clonal expansion and immune landscape changes in CD8⁺ T cells. We further showed that Grm4^−/− intrinsically activated interferon-γ production in CD8⁺

SUBMITTER: Wan Z 

PROVIDER: S-EPMC8664261 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature