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IL-9 Promotes the Survival and Function of Human Melanoma-Infiltrating CD4(+) CD8(+) Double-Positive T Cells

IL-9 Promotes the Survival and Function of Human Melanoma-Infiltrating CD4(+) CD8(+) Double-Positive T Cells

Tiphaine Parrot, Mathilde Allard, Romain Oger, Houssem Benlalam, Diane Raingeard de la Blétière, Anne Coutolleau, Laurence Preisser, Juliette Desfrançois, Amir Khammari, Brigitte Dréno, Nathalie Labarrière, etc.

Eur J Immunol. 2016 Jul;46(7):1770-82.

PMID: 27094152

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248756	IL-9 human			Price

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