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

L. Lyngaa, N.W. Pedersen, D. Schrama, C.A. Thrue, D. Ibrani, O. Met, P. Thor Straten, P. Nghiem, JC Becker, Sine Reker Hadrup

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Abstract

Merkel 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.
To 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.
In 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.
These T-cell epitopes represent ideal targets for antigen specific immune therapy of MCC, and enables tracking and characterisation of MCPyV specific immune responses.
Original languageEnglish
JournalJournal for ImmunoTherapy of Cancer
Volume2
Issue numberSuppl 2
Pages (from-to)P20
ISSN2051-1426
DOIs
Publication statusPublished - 2014
Externally publishedYes
Event1st Immunotherapy of Cancer Conference (ITOC1) - Munich, Germany
Duration: 12 Mar 201414 Mar 2014

Conference

Conference1st Immunotherapy of Cancer Conference (ITOC1)
Country/TerritoryGermany
CityMunich
Period12/03/201414/03/2014

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