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Open Access 16-12-2022 | Research

The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer

Authors: Saskia J. Santegoets, Marij J. P. Welters, Deborah S. Schrikkema, Manon R. Freriks, Hanna Kok, Bianca Weissbrich, Anouk van den Branden, Carsten Linnemann, Ton N. Schumacher, Sabina Adhikary, Gavin Bendle, Sjoerd H. van der Burg

Published in: Cancer Immunology, Immunotherapy | Issue 6/2023

Abstract

Immunotherapies targeting truly tumor-specific targets focus on the expansion and activation of T cells against neoantigens or oncogenic viruses. One target is the human papilloma virus type 16 (HPV16), responsible for several anogenital cancers and oropharyngeal carcinomas. Spontaneous and vaccine-induced HPV-specific T cells have been associated with better clinical outcome. However, the epitopes and restriction elements to which these T cells respond remained elusive. To identify CD8⁺ T cell epitopes in cultures of tumor infiltrating lymphocytes, we here used multimers and/or a functional screening platform exploiting single HLA class I allele-engineered antigen presenting cells. This resulted in the detection of 20 CD8⁺ T cell responses to 11 different endogenously processed HLA-peptide combinations within 12 HPV16-induced tumors. Specific HLA-peptide combinations dominated the response in patients expressing these HLA alleles. T cell receptors (TCRs) reactive to seven different HLA class I-restricted peptides could be isolated and analysis revealed tumor reactivity for five of the six TCRs analyzed. The tumor reactive TCRs to these dominant HLA class I peptide combinations can potentially be used to engineer tumor-specific T cells for adoptive cell transfer approaches to treat HPV16-induced cancers.

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Title: The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer
Authors: Saskia J. Santegoets
Marij J. P. Welters
Deborah S. Schrikkema
Manon R. Freriks
Hanna Kok
Bianca Weissbrich
Anouk van den Branden
Carsten Linnemann
Ton N. Schumacher
Sabina Adhikary
Gavin Bendle
Sjoerd H. van der Burg
Publication date: 16-12-2022
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 6/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-022-03350-x

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