Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer Predicts the Efficacy of a FOLFOX-Bevacizumab Drug Treatment Regimen.
Fiche publication
Date publication
septembre 2016
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain, Pr DELMAS Dominique, Pr GHIRINGHELLI François, Dr LADOIRE Sylvain, Dr VINCENT Julie, Dr VEGRAN Frédérique, Dr LIMAGNE Emeric, Dr DERANGERE Valentin, Dr THIBAUDIN Marion
Tous les auteurs :
Limagne E, Euvrard R, Thibaudin M, Rébé C, Derangère V, Chevriaux A, Boidot R, Végran F, Bonnefoy N, Vincent J, Bengrine-Lefevre L, Ladoire S, Delmas D, Apetoh L, Ghiringhelli F
Lien Pubmed
Résumé
Host immunity controls the development of colorectal cancer, and chemotherapy used to treat colorectal cancer is likely to recruit the host immune system at some level. Athough preclinical studies have argued that colorectal cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin, exert such effects, their combination as employed in the oncology clinic has not been evaluated. Here, we report the results of prospective immunomonitoring of 25 metastatic colorectal cancer (mCRC) patients treated with a first-line combination regimen of 5-FU, oxaliplatin, and bevacizumab (FOLFOX-bevacizumab), as compared with 20 healthy volunteers. Before this therapy was initiated, T regulatory cells (Treg), Th17, and granulocytic myeloid-derived suppressor cells (gMDSC) were increased significantly in mCRC, but only a high level of gMDSC was associated with a poor prognosis. Chemotherapy modulated the Treg/Th17 balance by decreasing Treg and increasing Th17 cell frequency by 15 days after the start of treatment. Increased Th17 frequency was associated with a poor prognosis. FOLFOX-bevacizumab treatment elicited a decrease in gMDSC in 15 of 25 patients and was associated with a better survival outcome. Notably, the gMDSCs that expressed high levels of PD-L1, CD39, and CD73 exerted a robust immunosuppressive activity, relative to other myeloid cells present in blood, which could be reversed by blocking the CD39/CD73 and PD-1/PD-L1 axes. Our work underscores the critical prognostic impact of early modifications in Th17 and gMDSC frequency in mCRC. Furthermore, it provides a clinical rationale to combine FOLFOX-bevacizumab chemotherapy with inhibitors of ATP ectonucleotidases and/or anti-PD-1/PD-L1 antibodies to more effectively treat this disease. Cancer Res; 76(18); 5241-52. ©2016 AACR.
Mots clés
Antineoplastic Combined Chemotherapy Protocols, administration & dosage, Bevacizumab, administration & dosage, Colorectal Neoplasms, drug therapy, Disease-Free Survival, Flow Cytometry, Fluorouracil, administration & dosage, Humans, Kaplan-Meier Estimate, Leucovorin, administration & dosage, Myeloid-Derived Suppressor Cells, immunology, Organoplatinum Compounds, administration & dosage, Polymerase Chain Reaction, Prospective Studies, Th17 Cells, immunology
Référence
Cancer Res.. 2016 Sep;76(18):5241-52