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Transcriptomic features of tumour-infiltrating CD4lowCD8high double positive αβ T cells in melanoma

Authors
  • Parrot, Tiphaine1, 2
  • Oger, Romain1, 2
  • Allard, Mathilde1, 2
  • Desfrançois, Juliette3
  • Raingeard de la Blétière, Diane4
  • Coutolleau, Anne4
  • Preisser, Laurence5
  • Khammari, Amir2, 6
  • Dréno, Brigitte2, 6
  • Delneste, Yves5
  • Guardiola, Philippe4
  • Fradin, Delphine1, 2
  • Gervois, Nadine1, 2
  • 1 Université de Nantes, Inserm, CRCINA, Nantes, F-44000, France , Nantes (France)
  • 2 LabEx IGO, Université de Nantes, Nantes, France , Nantes (France)
  • 3 Cytometry Facility «CytoCell», Federative Structure Research François Bonamy, Nantes, France , Nantes (France)
  • 4 Centre Hospitalier Universitaire, Angers, France , Angers (France)
  • 5 Université d’Angers, Inserm, CRCINA, Nantes, F-44000, France , Nantes (France)
  • 6 Université de Nantes, CHU Nantes, Inserm, CRCINA, Nantes, F-44000, France , Nantes (France)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Apr 03, 2020
Volume
10
Issue
1
Identifiers
DOI: 10.1038/s41598-020-62664-x
Source
Springer Nature
License
Green

Abstract

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 CD4lowCD8high 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.

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