[Impact of chemotherapies on immunosuppression and discovery of new therapeutic targets].

MDSC (myeloid derived suppressor cells) are immature cells from myeloid origin that accumulate in spleen and tumor bed during tumor growth and that can suppress anti-tumor immunity by various ways. Two chemotherapeutic agents, 5-fluorouracil and gemcitabin, that are commonly used in the treatment of colon cancer and pancreatic cancer, can selectively kill MDSC. Beneficial effects of 5-Fluorouracil and gemcitabin are however temporary. After treatment with those chemotherapies, an activation of the NLRP3 inflammasome is observed in MDSC, due to an interaction between cathepsin B and NLRP3, which leads to the production of IL-1β thus increasing pro-tumor immune responses. IL-1β enhances the production of IL-17 by CD4 T cells which in turn favors angiogenesis and tumor growth.