| Title: |
Transcriptomic features of tumour- infiltrating CD4 low CD8 high double positive αβ T cells in melanoma |
| Authors: |
Parrot, Tiphaine; Oger, Romain; Allard, Mathilde; Desfrançois, Juliette; Raingeard de La Blétìère, Diane; Coutolleau, Anne; Preisser, Laurence; Khammari, Amir; Dréno, Brigitte; Delneste, Yves; Guardiola, Philippe; Fradin, Delphine; Gervois, Nadine |
| Contributors: |
Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3); Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); LabEX IGO Immunothérapie Grand Ouest; Nantes Université (Nantes Univ); Nuclear Oncology (CRCINA-ÉQUIPE 13); Plateforme CYTOCELL Nantes (CRCINA-CYTOCELL); Centre Hospitalier Universitaire d'Angers (CHU Angers); Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7); Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2); Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4); Cancéropôle Grand OuestRégion Pays de la LoireLigue Nationale contre le Cancer; ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011) |
| Source: |
ISSN: 2045-2322. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2020 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
[SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; Peripheral CD4 + CD8 + double positive (DP) T cells are a phenotypically and functionally heterogeneous population depending on their origin and pathologic context. We previously identified among tumour infiltrating lymphocytes in melanoma, a tumour-reactive MHC class-I restricted CD4 low CD8 high DP αβ T-cell subpopulation with CD4-like function. In this study, we used an in-depth comparative transriptomic analysis of intra-melanoma DP T cells and CD4 and CD8 single positive (SP) T cells, to better comprehend the origin of this DP phenotype, and define the transcriptomic signature of activated DP T cells. We observed that intra-melanoma DP T cells were transcriptome-wise closer to their CD8 SP T-cell counterparts in terms of number of genes differentially expressed (97 in common with CD8 SP T cells and 15 with CD4 SP T cells) but presented hallmarks of a transition to a CD4-like functional profile (CD40LG) with a decreased cytotoxic signature (KLRC1) in favour of an increased cytokine-receptor interaction signature (IL4, IL24, IL17A…). This unleashed CD4-like program could be the results of the observed unbalanced expression of the THPOK/Runx3 transcription factors in DP T cells. Overall, this study allow us to speculate that intra-melanoma DP T cells arise from CD8 SP T cells being reprogrammed to a helper function. Contrary to the CD4 + CD8 + double positive (DP) thymocytes, well described as a T cell development stage, peripheral DP αβ T cells had attracted less attention mostly because of their weak frequency in the peripheral blood of healthy human donors (1 to 3%) 1,2. Nonetheless, following diverse inflammatory processes from viral or parasitic infections 3-5 , to autoimmune diseases 6,7 or cancer 8-14 , this subpopulation can become quite predominant in the blood or in the inflamed tissue/organ. This suggests a causal relationship between DP T cell emergence and disease. From these studies, DP T cells appeared as a more heterogeneous population than initially thought. Based on ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/32246006; PUBMED: 32246006 |
| DOI: |
10.1038/s41598-020-62664-x |
| Availability: |
https://inserm.hal.science/inserm-02534481; https://inserm.hal.science/inserm-02534481v1/document; https://inserm.hal.science/inserm-02534481v1/file/Parrot2020Eq3.pdf; https://doi.org/10.1038/s41598-020-62664-x |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.652B6559 |
| Database: |
BASE |