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- Title
The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer.
- Authors
Santegoets, Saskia J.; Welters, Marij J. P.; Schrikkema, Deborah S.; Freriks, Manon R.; Kok, Hanna; Weissbrich, Bianca; van den Branden, Anouk; Linnemann, Carsten; Schumacher, Ton N.; Adhikary, Sabina; Bendle, Gavin; van der Burg, Sjoerd H.
- 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.
- Subjects
T cells; HUMAN papillomavirus; T cell receptors; TUMOR-infiltrating immune cells; ANTIGEN presenting cells
- Publication
Cancer Immunology, Immunotherapy, 2023, Vol 72, Issue 6, p1553
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-022-03350-x