| Added by | mollevi |
|---|---|
| Last modified by | Nathalie Bonnefoy |
| Group name | EquipeNB |
| Item Type | Journal Article |
| Title | Accumulation of MDSC and Th17 cells in patients with metastatic colorectal cancer predict the efficacy of a FOLFOX-bevacizumab drug treatment regimen |
| Creator | Limagne et al. |
| Author | E. Limagne |
| Author | R. Euvrard |
| Author | M. Thibaudin |
| Author | C. Rebe |
| Author | V. Derangere |
| Author | A. Chevriaux |
| Author | R. Boidot |
| Author | F. Vegran |
| Author | N. Bonnefoy |
| Author | J. Vincent |
| Author | L. Bengrine |
| Author | S. Ladoire |
| Author | D. Delmas |
| Author | L. Apetoh |
| Author | F. Ghiringhelli |
| Abstract | Host immunity controls the development of colorectal cancer (CRC) and chemotherapy used to treat CRC is likely to recruit the host immune system at some level. While preclinical studies have argued that CRC drugs such as 5-fluorouracil 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 CRC patients treated with a first-line combination regimen of 5-fluorouracil, oxaliplatin and bevacizumab (FOLFOX-bevacizumab), as compared to 20 healthy volunteers. Before this therapy was initiated, TReg, Th17 and granulocytic MDSC (gMDSC) were increased significantly in metastatic CRC, 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 15/25 patients and was associated with a better survival outcome. Notably, gMDSC which 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 metastatic CRC. Further, 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. |
| Publication | Cancer Res |
| Date | Aug 5 2016 |
| Journal Abbr | Cancer research |
| DOI | 10.1158/0008-5472.CAN-15-3164 |
| ISSN | 1538-7445 (Electronic) 0008-5472 (Linking) |
| Tags | original |
| Date Added | 2018/11/14 - 12:04:32 |
| Date Modified | 2019/05/28 - 21:22:55 |
| Notes and Attachments | (Note) (Note) 27496709 (Attachment) |
Institut de Recherche en Cancérologie de
