Transcriptomic features of tumour-infiltrating CD4 low CD8 high double positive αβ T cells in melanoma

• Published in: Scientific reports 2020-04, Vol.10 (1), p.5900
• Main Authors: Parrot, Tiphaine, Oger, Romain, Allard, Mathilde, Desfrançois, Juliette, Raingeard de la Blétière, Diane, Coutolleau, Anne, Preisser, Laurence, Khammari, Amir, Dréno, Brigitte, Delneste, Yves, Guardiola, Philippe, Fradin, Delphine, Gervois, Nadine
• Format: Article
• Language: English
• Subjects: Cancer; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Plasticity - genetics; Cell Plasticity - immunology; Cellular Reprogramming - genetics; Cellular Reprogramming - immunology; Core Binding Factor Alpha 3 Subunit - metabolism; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Neoplastic - immunology; Humans; Life Sciences; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Melanoma - genetics; Melanoma - immunology; Melanoma - secondary; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Transcription Factors - metabolism; Transcriptome - immunology; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62664-x

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 CD8 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.