Transcriptomic features of tumour-infiltrating CD4lowCD8high double positive αβ T cells in melanoma
Tiphaine Parrot, Romain Oger, Mathilde Allard, Juliette Desfrançois, Diane Raingeard de la Blétière, Anne Coutolleau, Laurence Preisser, Amir Khammari, Brigitte Dréno, Yves Delneste, Philippe Guardiola, Delphine Fradin, Nadine Gervois
Abstract
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 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.