Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response
Aran, Andrea (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Lázaro Bermejo, Gonzalo (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Marco, Vicente (Hospital Quironsalud Barcelona)
Molina, Elisa (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Abancó, Ferran (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Peg, Vicente (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Gión, María (Hospital Universitario Ramón y Cajal (Madrid))
Garrigós Cubells, Laia (Quironsalud Group (Barcelona))
Pérez-García, José (Pangaea Oncology. Medical Scientia Innovation Research (MedSIR))
Cortés Castán, Javier (Universidad Europea de Madrid)
Martí, Mercè (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2023
Description:	15 pàg.
Abstract:	Introduction: 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. Methods: 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. Results: 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. Discussion: 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Breast cancer ; CD4+ T cells ; CD8+ T cells ; T cell receptor ; Tumor-infiltrating lymphocytes ; SDG 3 - Good Health and Well-being
Published in:	Frontiers in immunology, Vol. 14 (2023) , p. 1227766, ISSN 1664-3224

DOI: 10.3389/fimmu.2023.1227766
PMID: 37600765

15 p, 2.0 MB

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Articles > Research articles
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