P29. T-cell responses to oncogenic Merkel cell polyomavirus proteins distinguish Merkel cell carcinoma patients from healthy donors

• Published in: Journal for immunotherapy of cancer Vol. 2; no. Suppl 2; p. P20
• Main Authors: Lyngaa, L, Pedersen, NW, Schrama, D, Thrue, CA, Ibrani, D, Met, O, thor Straten, P, Nghiem, P, Becker, JC, Hadrup, SR
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 12.03.2014; BioMed Central Ltd; BioMed Central
• Subjects: Antigens; Poster Presentation; Skin cancer
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/2051-1426-2-S2-P20

PurposeMerkel cell carcinoma (MCC) is a highly aggressive skin cancer with strong evidence for viral carcinogenesis. The association of MCC with the Merkel cell polyomavirus (MCPyV) may explain the explicit immunogenicity of MCC. Indeed, MCPyV-encoded proteins are likely targets for cytotoxic immune responses to MCC as they are both foreign to the host and necessary to maintain the oncogenic phenotype. However, to date only a single MCPyV-derived CD8 T-cell epitope have been described, thus impeding specific monitoring of T-cell responses to MCC.MethodTo overcome this limitation, we scanned the MCPyV oncoproteins large T and small T antigen and the virus-capsid protein VP1 for potential T-cell epitopes, and tested for major histocompatibility complex (MHC) class I affinity. We confirmed the relevance of these epitopes using a high-throughput platform for T-cell enrichment and combinatorial encoding of MHC class I multimers.ResultsIn peripheral blood from 38 MCC patients and 30 healthy donors we identified 53 MCPyV-directed CD8+ T-cell responses against 35 different peptide sequences. Strikingly, T-cell responses against oncoproteins were exclusively present in MCC patients, but not in healthy donors. We further demonstrate both the processing and presentation of the oncoprotein-derived epitopes, as well as the lytic activity of oncoprotein-specific T cells towards MHC-matched MCC cells. Demonstrating the presence of oncoprotein-specific T cells among tumour infiltrating lymphocytes ex vivo further substantiated the relevance of the identified epitopes.ConclusionThese T-cell epitopes represent ideal targets for antigen specific immune therapy of MCC, and enables tracking and characterisation of MCPyV specific immune responses.