T cell recognition of large T and small T antigen in Merkel cell polyomavirus-associated cancer

Ulla Kring Hansen, Rikke Birgitte Lyngaa, Per Thor Straten, Jörgen C. Becker, Paul Nghiem, Sine Reker Hadrup

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    Abstract

    Merkel Cell Carcinoma is an aggressive human skin cancer induced by Merkel Cell Polyomavirus (MCPyV). MCPyV is commonly found in human, but the oncogenic transformation takes place during immunosuppression. Two mutation events allow the clonal integration of the viral genome into the host genome and translation of the two viral genes large T (LTA) and small T antigen (STA). Standard treatment with chemotherapy shows poor clinical outcome instead immunotherapy offers new potential treatment strategies. The use of PD-1 checkpoint inhibi-tors has shown promising results (>50% response rates, RECIST). However, not all patients are able to mount an immune response. Instead adoptive transfer of MCPyV-reactive T cells is an attractive strategy for this cohort. We have previously identified T cell epitopes from the MCPyV-derived proteins LTA, STA and VP1. Here we aim to expand the knowledge about T cell epitopes by including a broader range of HLA restrictions. We analyzed 31 patients’ peripheral blood mononuclear cells through enrichment of low frequency clones, followed by revealing of T cell reactivity using combinatorial color-encoded peptide-MHC multimers. 28 T cell responses against 18 MCPyV-derived peptides were detected. Addi-tional testing has confirmed functional T cell reactivity against one of these epitopes. We analyzed 3 patients’ tumor infiltrating lymphocytes by direct ex-vivo detection of T cell reactivity using combinatorial color-encoded peptide-MHC multimers. 5 T cell responses against 5 peptides were detected. The functional T cell response towards detected epitopes is under investigation in order to characterize them as potential T cell targets in a new therapy.
    Original languageEnglish
    Publication date2017
    Publication statusPublished - 2017
    Event44th Scandinavian Society for Immunology Meeting - Clarion Hotel Sign, Stockholm, Sweden
    Duration: 17 Oct 201720 Oct 2017
    Conference number: 44
    http://www.ssi2017.se/

    Conference

    Conference44th Scandinavian Society for Immunology Meeting
    Number44
    LocationClarion Hotel Sign
    Country/TerritorySweden
    CityStockholm
    Period17/10/201720/10/2017
    Internet address

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