NLRP3 deficiency reverts intratumoral T cell exhaustion

CD8+ T cells derived from mice with intact NLRP3 signaling in the tumor microenvironment showed an increased expression of coinhibitory receptors PD-1, TIM-3, 2B4 and LAG-3 compared to CD8+ T cells from PancOVA-bearing Nlrp3-/- mice, indicating that NLRP3 inflammasome activation in the tumor microenvironment mediates IL-18 receptor signaling-induced T cell exhaustion. RNAseq was used to characterised molecular pathways involved in T cell plasticity in the presence and absence of intratumoral NLRP3. RNAseq of endogenous WT versus Nlrp3-/- CTLs showed a distinct transcriptional program for WT and Nlrp3-/- CTLs, related to signaling pathways regulating T cell exhaustion