Abstract 3597
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Editorial acknowledgement
Legal entity responsible for the study
University Hospital of Besançon.
Funding
Besancon University Hospital, Ligue Contre le cancer Grand-Est and Association Nationale de la Recherche et de la Technologie.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2036 - Salivary metabolomics for colorectal cancer detection
Presenter: Hiroshi Kuwabara
Session: Poster Display session 3
Resources:
Abstract
1868 - Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
Presenter: Veronika Voronova
Session: Poster Display session 3
Resources:
Abstract
3655 - Liquid biopsy assays using combined circulating tumor cells and circulating tumor DNA in the same patients for the diagnosis of primary lung cancer
Presenter: Yongjoon Suh
Session: Poster Display session 3
Resources:
Abstract
3685 - Peripheral Cytotoxic T Cell Correlates with Tumor Mutational Burden and is Predictive for Progression Free Survival in Advanced Breast Cancer
Presenter: Xiao-ran Liu
Session: Poster Display session 3
Resources:
Abstract
1050 - Splenic Metabolic Activity as Biomarker in Cervical Cancer
Presenter: Emiel De Jaeghere
Session: Poster Display session 3
Resources:
Abstract
1413 - Identification of distinct subtypes revealing prognostic and therapeutic relevance in diffuse type gastric cancer
Presenter: Seon-Kyu Kim
Session: Poster Display session 3
Resources:
Abstract
2140 - Recurrence risk evaluation in stage IB/IIA gastric cancer with TP53 codon 72 polymorphisms
Presenter: Satoshi Nishizuka
Session: Poster Display session 3
Resources:
Abstract
1573 - Identification and validation of a prognostic 4 genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
Presenter: Yongcong Yan
Session: Poster Display session 3
Resources:
Abstract
1196 - Plasma KIM-1 is associated with clinical outcomes after resection for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)
Presenter: Wenxin Xu
Session: Poster Display session 3
Resources:
Abstract
2657 - Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
Presenter: Katharina Nekolla
Session: Poster Display session 3
Resources:
Abstract