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.

Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients.

The controlled contact between two micro-sized objects, such as beads and cells, and the assessment of their adhesion status is demonstrated in this research. The controlled contact is carried out in a microfluidic channel under flow conditions and makes use of a combination of hydrodynamic traps, flow drag force and dielectrophoretic (DEP) force to maintain the two objects in contact for the desired duration in a first step. Then, the pair objects are separated in the second step in order to explore their adhesion status. Adhesion events are mediated by the bond formed between a receptor and its ligand, and their binding kinetic parameters can be extracted from the measurements using the proposed device.