Resistance to Chemotherapy on Tumor Through Cathepsin B-dependent Activation of the NLRP3 Inflammasome

ABSTRACT

Anticancer drugs kill tumor cells and increase host anti-tumor immunity. Interestingly, gemcitabin (Gem) and 5-fluorouracil (5-FU), widely used anticancer drugs, lead to IL-1beta secretion releasing cathepsin B which activates Nlrp3 inflammasome in myeloid derived suppressor cells (MDSCs). MDSC derived IL-1beta enhance secretion of IL-17 by CD4+ T cells. This mechanism limits the antitumor efficacy of the drugs and promotes tumor growth.