Data from T Cells Expressing Receptor Recombination/Revision Machinery Are Detected in the Tumor Microenvironment and Expanded in Genomically Over-unstable Models
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Le résumé fourni par la source
Abstract Tumors undergo dynamic immunoediting as part of a process that balances immunologic sensing of emerging neoantigens and evasion from immune responses. Tumor-infiltrating lymphocytes (TIL) comprise heterogeneous subsets of peripheral T cells characterized by diverse functional differentiation states and dependence on T-cell receptor (TCR) specificity gained through recombination events during their development. We hypothesized that within the tumor microenvironment (TME), an antigenic milieu and immunologic interface, tumor-infiltrating peripheral T cells could reexpress key elements of the TCR recombination machinery, namely, Rag1 and Rag2 recombinases and Tdt polymerase, as a potential mechanism involved in the revision of TCR specificity. Using two syngeneic invasive breast cancer transplantable models, 4T1 and TS/A, we observed that Rag1, Rag2, and Dntt in situ mRNA expression characterized rare tumor-infiltrating T cells. In situ expression of the transcripts was increased in coisogenic Mlh1-deficient tumors, characterized by genomic overinstability, and was also modulated by PD-1 immune-checkpoint blockade. Through immunolocalization and mRNA hybridization analyses, we detected the presence of rare TDT+RAG1/2+ cells populating primary tumors and draining lymph nodes in human invasive breast cancer. Analysis of harmonized single-cell RNA-sequencing data sets of human cancers identified a very small fraction of tumor-associated T cells, characterized by the expression of recombination/revision machinery transcripts, which on pseudotemporal ordering corresponded to differentiated effector T cells. We offer thought-provoking evidence of a TIL microniche marked by rare transcripts involved in TCR shaping.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Data from T Cells Expressing Receptor Recombination/Revision Machinery Are Detected in the Tumor Microenvironment and Expanded in Genomically Over-unstable Models
- Date Crossref
- 04/04/2023
- Éditeur
- American Association for Cancer Research (AACR)
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Palermo Tumor Immunology Unit pays non établi dans la noticeUniversité ou école supérieure
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National Research Council pays non établi dans la noticeOrganisation à but non lucratif
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Candiolo Cancer Institute pays non établi dans la noticeOrganisation à but non lucratif
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Istituti di Ricovero e Cura a Carattere Scientifico pays non établi dans la noticeÉtablissement de santé
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Fondazione IRCCS Istituto Nazionale dei Tumori pays non établi dans la noticeÉtablissement de santé
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IFOM pays non établi dans la noticeStructure de recherche
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University of Torino Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
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Molecular Immunology Unit pays non établi dans la noticeInstitution
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Computational Genomics Laboratory pays non établi dans la noticeStructure de recherche
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Institute of Molecular Genetics "Luigi Luca Cavalli Sforza pays non établi dans la noticeStructure de recherche
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Molecular Targeting Unit pays non établi dans la noticeInstitution
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Department of Pathology and Laboratory Medicine pays non établi dans la noticeStructure de recherche
Tumor Immunology Unit — University of Palermo, National Research Council et Candiolo Cancer Institute, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.