4-1BB stimulation with concomitant inactivation of adenosine A2B receptors enhances CD8+ T cell antitumor response.

ABSTRACT: Activating the immune costimulatory receptor 4-1BB (CD137) with agonist antibody binding and crosslinking-inducing agents that elicit 4-1BB intracellular signaling potentiates the antitumor responses of CD8+ T cells. However, the underlying in-depth mechanisms remain to be defined. Here, we show that agonistic 4-1BB treatment of activated CD8+ T cells under continuous antigenic stimulation makes them more metabolically vulnerable to redox perturbation by ablation of intracellular glutathione (GSH) and glutathione peroxidase 4 (GPX4) inhibition. Further, genetic deletion of adenosine A2B receptor (A2BR) induces superior survival and expansion advantage of competent CD8+ T cells with agonistic 4-1BB costimulation, leading to more effective antitumor efficacy of adoptive cell therapy (ACT). M

SUBMITTER: Ahn J 

PROVIDER: S-EPMC12126218 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature