{"doi":"10.3389/fimmu.2023.1227766","title":"Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response","abstract":"<jats:sec><jats:title>Introduction</jats:title><jats:p>Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic value in breast cancer (BC) and exert a protective function against tumor growth, indicating that it is susceptible to treatment using adoptive cell transfer of TILs or T cell receptor (TCR)-based therapies. TCR can be used to identify naturally tumor-reactive T cells, but little is known about the differences in the TCR repertoires of CD4+ and CD8+ TILs.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>TCR high-throughput sequencing was performed using TILs derived from the initial cultures of 11 BC biopsies and expanded and sorted CD4+ and CD8+ TILs as well as using PBMCs from healthy donors expanded and sorted using the same methodology.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Physicochemical TCR differences between T cell subsets were observed, as CD4+ TILs presented larger N(D)Nnt TRB sequences and with a higher usage of positively charged residues, although only the latest was also observed in peripheral T cells from healthy individuals. Moreover, in CD4+ TILs, a more restricted TCR repertoire with a higher abundance of similar sequences containing certain amino acid motifs was observed.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Some differences between CD4+ and CD8+ TCRs were intrinsic to T cell subsets as can also be observed in peripheral T cells from healthy individuals, while other were only found in TILs samples and therefore may be tumor-driven. Notably, the higher similarity among CD4+ TCRs suggests a higher TCR promiscuity in this subset.</jats:p></jats:sec>","journal":"Frontiers in Immunology","year":2023,"id":589507,"datarank":0.47600732856195416,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.1306195646128472,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.1306195646128472,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":8,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1508271,"name":"Gonzalo Lázaro","orcid":null,"position":1,"is_corresponding":false},{"id":1508272,"name":"Vicente Marco","orcid":null,"position":2,"is_corresponding":false},{"id":1508273,"name":"Elisa Molina","orcid":null,"position":3,"is_corresponding":false},{"id":1508274,"name":"Ferran Abancó","orcid":null,"position":4,"is_corresponding":false},{"id":849980,"name":"Vicente Peg","orcid":"0000-0002-5203-6166","position":5,"is_corresponding":false},{"id":1508275,"name":"María Gión","orcid":null,"position":6,"is_corresponding":false},{"id":1508276,"name":"Laia Garrigós","orcid":null,"position":7,"is_corresponding":false},{"id":1508277,"name":"José Pérez-García","orcid":null,"position":8,"is_corresponding":false},{"id":303791,"name":"Javier Cortés","orcid":"0000-0001-7623-1583","position":9,"is_corresponding":false},{"id":1508278,"name":"Mercè Martí","orcid":null,"position":10,"is_corresponding":false},{"id":1508270,"name":"Andrea Aran","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response","abstract":"<jats:sec><jats:title>Introduction</jats:title><jats:p>Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic value in breast cancer (BC) and exert a protective function against tumor growth, indicating that it is susceptible to treatment using adoptive cell transfer of TILs or T cell receptor (TCR)-based therapies. TCR can be used to identify naturally tumor-reactive T cells, but little is known about the differences in the TCR repertoires of CD4+ and CD8+ TILs.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>TCR high-throughput sequencing was performed using TILs derived from the initial cultures of 11 BC biopsies and expanded and sorted CD4+ and CD8+ TILs as well as using PBMCs from healthy donors expanded and sorted using the same methodology.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Physicochemical TCR differences between T cell subsets were observed, as CD4+ TILs presented larger N(D)Nnt TRB sequences and with a higher usage of positively charged residues, although only the latest was also observed in peripheral T cells from healthy individuals. Moreover, in CD4+ TILs, a more restricted TCR repertoire with a higher abundance of similar sequences containing certain amino acid motifs was observed.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Some differences between CD4+ and CD8+ TCRs were intrinsic to T cell subsets as can also be observed in peripheral T cells from healthy individuals, while other were only found in TILs samples and therefore may be tumor-driven. 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