{"doi":"10.1126/sciadv.adm7515","title":"CD8 <sup>+</sup> T cell targeting of tumor antigens presented by HLA-E","abstract":"The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors on NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression by cancer cells can be targeted for MHC-E–restricted T cell control, we immunized rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors genetically programmed to elicit MHC-E–restricted CD8 + T cells and to express established tumor-associated antigens (TAAs) including prostatic acidic phosphatase (PAP), Wilms tumor-1 protein, or Mesothelin. T cell responses to all three tumor antigens were comparable to viral antigen-specific responses with respect to frequency, duration, phenotype, epitope density, and MHC restriction. Thus, CMV-vectored cancer vaccines can bypass central tolerance by eliciting T cells to noncanonical epitopes. We further demonstrate that PAP-specific, MHC-E–restricted CD8 + T cells from RhCMV/PAP-immunized RM respond to PAP-expressing HLA-E + prostate cancer cells, suggesting that the HLA-E/NKG2A immune checkpoint can be exploited for CD8 + T cell–based immunotherapies.","journal":"Science Advances","year":2024,"id":422953,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":656732,"name":"Marieke C. 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Selseth","orcid":"0000-0001-9536-463X","position":10,"is_corresponding":false},{"id":656734,"name":"Nessy John","orcid":"0000-0002-4114-4946","position":11,"is_corresponding":false},{"id":846407,"name":"Tin Htwe Thin","orcid":"0000-0002-7891-1459","position":12,"is_corresponding":false},{"id":1217906,"name":"Siarhei Dzedzik","orcid":null,"position":13,"is_corresponding":false},{"id":217933,"name":"Colin Havenar‐Daughton","orcid":"0000-0002-2880-3927","position":14,"is_corresponding":false},{"id":263668,"name":"Michael K. Axthelm","orcid":"0000-0002-1984-5906","position":15,"is_corresponding":false},{"id":1217907,"name":"Janet L. Douglas","orcid":null,"position":16,"is_corresponding":false},{"id":59438,"name":"Alan J. Korman","orcid":"0000-0002-1142-8542","position":17,"is_corresponding":false},{"id":86525,"name":"Nina Bhardwaj","orcid":"0000-0003-1865-4187","position":18,"is_corresponding":false},{"id":72996,"name":"Ashutosh Tewari","orcid":"0000-0002-3146-4524","position":19,"is_corresponding":false},{"id":263667,"name":"Scott G. Hansen","orcid":"0000-0002-9845-6481","position":20,"is_corresponding":false},{"id":472911,"name":"Daniel Malouli","orcid":"0000-0003-1287-7283","position":21,"is_corresponding":false},{"id":246463,"name":"Louis J. 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