Glutamate receptor-T cell receptor signaling potentiates full CD8⁺ T cell activation and effector function in tumor immunity.

ABSTRACT: Glutamate is best known as an excitatory neurotransmitter. However, its roles in T cell immunity remain underrecognized. We investigated the interplay between glutamate receptors (GluRs) and T cell receptors (TCRs) during CD8⁺ T cell activation. Our findings reveal that GluR expression in CD8⁺ T lymphocytes strongly correlates with the activation of TCR-CD28 signaling, enhancing their antitumor effector responses. Conversely, pharmacologic antagonism of GluRs in activated CD8⁺ T cells disrupts the colocalization of GluR with TCRVβ8.1, reduces the phosphorylation of TCR-signaling intermediates, alters calcium flux, and impairs the metabolic switch to glycolysis essential for T cell activation. Moreover, these disruptions blunt clonal proliferation and compro

SUBMITTER: de Aquino MTP 

PROVIDER: S-EPMC12529521 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature