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Eur J Immunol. 2016 Jul;46(7):1770-82. doi: 10.1002/eji.201546061. Epub 2016 May 6.

IL-9 promotes the survival and function of human melanoma-infiltrating CD4(+) CD8(+) double-positive T cells.

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INSERM, U892, Nantes, France.
CNRS, UMR 6299, Nantes, France.
Université de Nantes, Nantes, France.
Université d'Angers, Angers, France.
SNP Transcriptome & Epigenomics Facility, Centre Hospitalier Universitaire, Angers, France.
Cytometry Facility "CytoCell", SFR François Bonamy, Nantes, France.
Unit of Skin Cancer, Centre Hospitalier Universitaire, Nantes, France.
GMP Unit of Cellular Therapy, Centre Hospitalier Universitaire, Nantes, France.


We previously demonstrated an accumulation of tumor-reactive CD4(+) CD8(+) double positive (DP) T cells within melanoma-infiltrating lymphocytes, supporting their role in the regulation of anti-tumor immune responses. Similarly to their CD8(+) counterparts, intra-tumor DP T cells are MHC class-I restricted but differed by a limited lytic activity against autologous melanoma cells. Based on these observations and to further characterize DP T cells, both populations were compared at the transcriptional level. Our results revealed the overexpression of the IL-9 receptor (IL-9R) by DP T cells and prompted us to investigate the impact of IL-9 on their biology. We show that IL-9 favors DP T-cell survival by protecting them from apoptosis and by promoting their proliferation. In addition, IL-9 enhances their ability to produce cytokines and increased their levels of granzyme B/perforin as well as degranulation capacity, leading to a strengthened cytotoxic activity against melanoma cells. Taken together, the IL-9R(high) DP T-cell population could be a new preferential target for IL-9, which could take part in their retention within the melanoma infiltrate while also favoring their anti-tumor activity. More generally, our results extend the pleiotropic effects of IL-9 to IL-9R-expressing intra-tumor T cells, which could further potentiate anti-tumor immune responses.


CD4+CD8+ double-positive T lymphocyte; IL-9; IL-9R; Melanoma; TIL

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