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

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 D...

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Published in:Scientific reports 2020-04, Vol.10 (1), p.5900-5900, Article 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:
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CD4 antigen
CD8 antigen
Cytotoxicity
Gene expression
Humanities and Social Sciences
Interleukin 1
Interleukin 24
Interleukin 4
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Melanoma
multidisciplinary
Phenotypes
Runx3 protein
Science
Science (multidisciplinary)
Transcription factors
Tumors
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-62664-x