Abstract
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.
Highlights
Anal squamous cell carcinoma (SCCA) is a rare disease accounting for 2.7% of gastrointestinal malignancies, but the incidence rate of this cancer is increasing each year worldwide [1]
We have recently shown that the addition of docetaxel to cisplatin plus 5-fluorouracil (DCF) might be an attractive strategy for advanced SCCA patients, generating high levels of long-term complete remissions (Epitopes-HPV02, NCT02402842) [4]
Magnitude of Anti-Telomerase-Specific T Helper 1 (TH1) Response was Increased in SCCA Patients Following DCF Chemotherapy
Summary
Anal squamous cell carcinoma (SCCA) is a rare disease accounting for 2.7% of gastrointestinal malignancies, but the incidence rate of this cancer is increasing each year worldwide [1]. Treatment of advanced SCCA remains a challenging issue since complete remission is a rare event, observed in less than 5% of cases and treatment of metastatic diseases are performed in a palliative setting. We have recently shown that the addition of docetaxel to cisplatin plus 5-fluorouracil (DCF) might be an attractive strategy for advanced SCCA patients, generating high levels of long-term complete remissions (Epitopes-HPV02, NCT02402842) [4]. 25% of the patients treated with DCF remained free of progression in an updated analysis of this study [5]. These promising results prompted us to explore the biological mechanisms underlying DCF efficacy
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