TIM-3 blockade leads to increased DNA sensing by cGAS–STING (by Kissiovd via Wikimedia Commons)
TIM-3 blocking antibodies, which are showing promise in cancer clinical trials, can reverse T-cell exhaustion, but their effects on other immune cells are less clear. de Mingo Pulido et al. show that blocking TIM-3 promotes HMGB1-dependent endocytosis of extracellular DNA by classical dendritic cells. This activates the cyclic GMP-AMP synthase (cGAS) and stimulator of IFN genes (STING) pathway, leading to type I IFN and subsequently CXCL9 production. This pathway is required for the antitumor effects of TIM-3 blockade and paclitaxel in a mouse breast cancer model. The study provides new understanding of the mechanisms underlying TIM-3–targeted therapy.
de Mingo Pulido Á, …, Ruffell B. Immunity 2021 Jun 8;54:1154–67.e7.
TRMs in the lungs provide a niche that promotes tumor progression (from Nephron via Wikimedia Commons)
Increased understanding of the diversity of macrophages in tumors is...