Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers

Abstract

Immune checkpoint blockers improve the overall survival of a limitednumber of patients among different cancers. Identifying pathways thatinfluence the immunological and clinical response to treatment is criticalto improve the therapeutic efficacy and predict clinical responses. Recently,a key role has been assigned to innate immune mechanisms in checkpointblockade-driven anti-tumor responses. However, inflammatory pathwayscan both improve and impair anti-tumor immunity. In this review, wediscuss how different inflammatory pathways, particularly inflammasomeactivation, can influence the clinical outcome of immune checkpoint blockers.Inflammasome activation may reinforce anti-tumor immunity by boostingCD8+ T cell priming as well as by enhancing T helper type 17 (Th17)responses. In particular, we focus on the modulation of the cation channeltransmembrane protein 176B (TMEM176B) and the ectonucleotidase CD39as potential targets to unleash inflammasome activation leading to reinforcedanti-tumor immunity and improved efficacy of immune checkpointblockers. Future studies should be aimed at investigating the mechanismsand cell subsets involved in inflammasome-driven anti-tumor responses.