Analysis of tumor infiltrating CD4+ and CD8+ CDR3 sequences reveals shared features putatively associated to the anti-tumor immune response

Frontiers in Immunology

Immunology

Gonzalo Lázaro¹  Andrea Aran¹  Ferran Abancó¹  Elisa Molina¹  Mercè Martí²  Laia Garrigós³  José Pérez-García⁴  Javier Cortés⁵  María Gión⁶  Vicente Peg⁷  Vicente Marco⁸ 

[1] Immunology Unit, Department of Cell Biology, Physiology, and Immunology, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain;Immunology Unit, Department of Cell Biology, Physiology, and Immunology, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain;Biosensing and Bioanalysis Group, Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Bellaterra, Spain;International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain;International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain;Medical Scientia Innovation Research (MedSIR), Barcelona, Spain;International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain;Medical Scientia Innovation Research (MedSIR), Barcelona, Spain;Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain;Medical Oncology Department, Ramón y Cajal University Hospital, Madrid, Spain;Pathology Department, Vall d’Hebron University Hospital, Barcelona, Spain;Department of Morphological Sciences, Universidad Autónoma de Barcelona, Bellaterra, Spain;Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain;Pathology, Hospital Quironsalud Barcelona, Barcelona, Spain;

关键词: tumor-infiltrating lymphocytes;    CD4+ T cells;    CD8+ T cells;    T cell receptor;    breast cancer;   

DOI  :  10.3389/fimmu.2023.1227766

 received in 2023-05-23, accepted in 2023-07-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionTumor-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.MethodsTCR 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.ResultsPhysicochemical 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.DiscussionSome 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.

【 授权许可】

Unknown   
Copyright © 2023 Aran, Lázaro, Marco, Molina, Abancó, Peg, Gión, Garrigós, Pérez-García, Cortés and Martí