Item Type: | Article |
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Title: | Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion |
Creators Name: | Giordano, M. and Henin, C. and Maurizio, J. and Imbratta, C. and Bourdely, P. and Buferne, M. and Baitsch, L. and Vanhille, L. and Sieweke, M.H. and Speiser, D.E. and Auphan-Anezin, N. and Schmitt-Verhulst, A.M. and Verdeil, G. |
Abstract: | T cells infiltrating neoplasms express surface molecules typical of chronically virus-stimulated T cells, often termed "exhausted" T cells. We compared the transcriptome of "exhausted" CD8 T cells infiltrating autochthonous melanomas to those of naïve and acutely stimulated CD8 T cells. Despite strong similarities between transcriptional signatures of tumor- and virus-induced exhausted CD8 T cells, notable differences appeared. Among transcriptional regulators, Nr4a2 and Maf were highly overexpressed in tumor-exhausted T cells and significantly upregulated in CD8 T cells from human melanoma metastases. Transduction of murine tumor-specific CD8 T cells to express Maf partially reproduced the transcriptional program associated with tumor-induced exhaustion. Upon adoptive transfer, the transduced cells showed normal homeostasis but failed to accumulate in tumor-bearing hosts and developed defective anti-tumor effector responses. We further identified TGF{beta} and IL-6 as main inducers of Maf expression in CD8 T cells and showed that Maf-deleted tumor-specific CD8 T cells were much more potent to restrain tumor growth in vivo. Therefore, the melanoma microenvironment contributes to skewing of CD8 T cell differentiation programs, in part by TGF{beta}/IL-6-mediated induction of Maf. |
Keywords: | Maf, Melanoma, T-Cell Exhaustion, TGF{beta}, Animals, Nice |
Source: | EMBO Journal |
ISSN: | 0261-4189 |
Publisher: | EMBO Press / Wiley |
Volume: | 34 |
Number: | 15 |
Page Range: | 2042-2058 |
Date: | 4 August 2015 |
Official Publication: | https://doi.org/10.15252/embj.201490786 |
PubMed: | View item in PubMed |
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