Anal squamous cell carcinoma (SCCA) is associated with E6 and E7 oncoproteins encoded by human papillomavirus (HPV) 16. Addition of Docetaxel to 5-Fluorouracil plus Cisplatin (DCF) induces favorable disease control and complete remission rate in recent clinical trials. Taking this observation into account, we decided to analyze the impact of DCF chemotherapy on adaptive immunity and immunosuppressive cells in SCCA.
Peripheral blood mononuclear cells from healthy donors and SCCA patients included in Epitopes-HPV01 and 02 studies were analyzed. The presence of T-cell responses after short term T-cell stimulation against HPV16-E6/E7 and TERT-antigens was measured by IFNγ-ELISpot. Immune checkpoint expression and immunosuppressive cells were monitored by flow cytometry.
We first observed an enhanced HPV-specific T-cell response following DCF chemotherapy. Our investigations also suggest that TERT might be a relevant antigen in HPV-driven cancers. TERT-restricted CD4 Th1 were correlated to E6 responses and also enhanced following DCF treatment of SCCA patients. The distribution of T-cell exhaustion markers on peripheral T lymphocytes unraveled a drop of CD226 expression and the emergence of CD226-TIGIT+ T-cell subset. Monocytic-myeloid-derived-suppressor cells (M-MDSC) and regulatory T-cell (Treg) rates were increased. Treg levels and T-cell exhaustion markers did not influence clinical outcomes and frequencies of specific immune responses. M-MDSC levels monitored after DCF chemotherapy were correlated with progression free survival and antigen-specific T-cell response intensity and diversity.
DCF chemotherapy did not impair antigen-specific T-cell responses, supporting the potential interest to combine DCF chemotherapy with immunotherapies. Moreover, our study identifies post-therapy M-MDSC as a prognostic factor in SCCA patients.
Clinical trial identification
Epitopes-HPV01: NCT01845779 Epitopes-HPV02: NCT02402842.
Legal entity responsible for the study
University Hospital of Besançon.
Besancon University Hospital, Ligue Contre le cancer Grand-Est and Association Nationale de la Recherche et de la Technologie.
All authors have declared no conflicts of interest.