Anti-Telomerase CD4 Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV
Fiche publication
Date publication
septembre 2020
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr BORG Christophe, Dr VERNEREY Dewi, Dr VIENOT Angélique, Dr KIM Stephano
Tous les auteurs :
Spehner L, Kim S, Vienot A, François E, Buecher B, Adotevi O, Vernerey D, Abdeljaoued S, Meurisse A, Borg C
Lien Pubmed
Résumé
Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic value of adaptive immune responses and immunosuppressive cells in SCCA patients included in two prospective studies (Epitopes-HPV01 and HPV02). The presence of T-cell responses against Human papillomavirus (HPV)16-E6/E7 and anti-telomerase (hTERT)-antigens was measured by IFNᵧ-ELISpot. Here, we showed that HPV-adaptive immune responses are increased in SCCA patients. SCCA patients also displayed enhanced circulating TH1 T-cells restricted by hTERT. Exposition to DCF increased hTERT immunity but not HPV or common viruses immune responses. Notably, the correlation of hTERT immune responses with SCCA patients' clinical outcomes highlights that hTERT is a relevant antigen in this HPV-related disease. The influence of peripheral immunosuppressive cells was investigated by flow cytometry. While both regulatory T-cells and monocytic-myeloid-derived suppressive cells (M-MDSC) accumulated in the peripheral blood of SCCA patients, only high levels of M-MDSC were negatively correlated with hTERT adaptive immune responses and predicted poor prognosis. Altogether, our results reveal that hTERT is a relevant antigen in HPV-driven SCCA disease and that M-MDSC levels influence TH1-adaptive immune responses and patients' survival.
Mots clés
Biomarkers, DCF chemotherapy, M-MDSC, advanced anal squamous cell carcinoma, hTERT antigens
Référence
Int J Mol Sci. 2020 Sep 17;21(18):