title: [Impact of chemotherapies on immunosuppression and discovery of new therapeutic targets].
abstract: 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.
authors.affiliation: INSERM U866, Facultés de médecine et de pharmacie, Centre de recherche, 7 Bd Jeanne-d'Arc, 21079 Dijon, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bruchard
authors.affiliation: INSERM U866, Facultés de médecine et de pharmacie, Centre de recherche, 7 Bd Jeanne-d'Arc, 21079 Dijon, France, Centre Georges-Francois-Leclerc, 21079 Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004852:Epoxy Compounds / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000209:etiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D002352:Carrier Proteins; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D058847:Inflammasomes; D020381:Interleukin-17; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C092940:cathestatin B; D003841:Deoxycytidine; D014443:Tyrosine; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: chemoresistant tumor; inflammasome; myeloid cells