Scientific reports, 2020-04, Vol.10 (1), p.5900
2020
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- Autor(en) / Beteiligte
- Titel
- Transcriptomic features of tumour-infiltrating CD4 low CD8 high double positive αβ T cells in melanoma
- Ist Teil von
- Scientific reports, 2020-04, Vol.10 (1), p.5900
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-020-62664-xTitel-ID: cdi_hal_primary_oai_HAL_inserm_02534481v1
- Format
- –
- Schlagworte
- 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