Anti-Inflammatory Drugs Remodel the Tumor Immune Environment to Enhance Immune Checkpoint Blockade Efficacy.

ABSTRACT: Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting the COX2/PGE₂/EP2-4 pathway with widely used nonsteroidal and steroidal anti-inflammatory drugs synergized with ICB in mouse cancer models. We exploited a bilateral surgery model to distinguish responders from nonresponders shortly after treatment and identified acute IFNγ-driven transcriptional remodeling in responder mice, which was also associated with patient benefit to ICB. Monotherapy with COX2 inhibitors or EP2-4 PGE₂ receptor antagonists rapidly induced this response program and, in combination with ICB, increased the intratumoral accumulation of effector T cells. Treatment of patient-derived tumor fragm

SUBMITTER: Pelly VS 

PROVIDER: S-EPMC7611767 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature