cathestatin-b and Neoplasms

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.

Topics: Animals; Carrier Proteins; CD4-Positive T-Lymphocytes; Deoxycytidine; Epoxy Compounds; Fluorouracil; Gemcitabine; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Inflammasomes; Interleukin-17; Interleukin-1beta; Mice; Myeloid Cells; Neoplasms; Neovascularization, Pathologic; NLR Family, Pyrin Domain-Containing 3 Protein; Tyrosine