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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.

Author information

1
INSERM, U892, Nantes, France.
2
CNRS, UMR 6299, Nantes, France.
3
Université de Nantes, Nantes, France.
4
Université d'Angers, Angers, France.
5
SNP Transcriptome & Epigenomics Facility, Centre Hospitalier Universitaire, Angers, France.
6
Cytometry Facility "CytoCell", SFR François Bonamy, Nantes, France.
7
Unit of Skin Cancer, Centre Hospitalier Universitaire, Nantes, France.
8
GMP Unit of Cellular Therapy, Centre Hospitalier Universitaire, Nantes, France.

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.

KEYWORDS:

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

PMID:
27094152
DOI:
10.1002/eji.201546061
[Indexed for MEDLINE]
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