IL-9 promotes the survival and function of human melanoma-infiltrating CD4(+) CD8(+) double-positive T cells.
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.
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.
Tiphaine
T
Parrot
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.
Mathilde
M
Allard
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.
Romain
R
Oger
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.
Houssem
H
Benlalam
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université d'Angers, Angers, France.|SNP Transcriptome & Epigenomics Facility, Centre Hospitalier Universitaire, Angers, France.
Diane
D
Raingeard de la Blétière
SNP Transcriptome & Epigenomics Facility, Centre Hospitalier Universitaire, Angers, France.
Anne
A
Coutolleau
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université d'Angers, Angers, France.
Laurence
L
Preisser
Cytometry Facility "CytoCell", SFR François Bonamy, Nantes, France.
Juliette
J
Desfrançois
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.|Unit of Skin Cancer, Centre Hospitalier Universitaire, Nantes, France.|GMP Unit of Cellular Therapy, Centre Hospitalier Universitaire, Nantes, France.
Amir
A
Khammari
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.|Unit of Skin Cancer, Centre Hospitalier Universitaire, Nantes, France.|GMP Unit of Cellular Therapy, Centre Hospitalier Universitaire, Nantes, France.
Brigitte
B
Dréno
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.
Nathalie
N
Labarrière
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université d'Angers, Angers, France.
Yves
Y
Delneste
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université d'Angers, Angers, France.|SNP Transcriptome & Epigenomics Facility, Centre Hospitalier Universitaire, Angers, France.
Philippe
P
Guardiola
INSERM, U892, Nantes, France.|CNRS, UMR 6299, Nantes, France.|Université de Nantes, Nantes, France.
Nadine
N
Gervois
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D016906:Interleukin-9 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053651:Receptors, Interleukin-9 / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D016906:Interleukin-9; D053651:Receptors, Interleukin-9
CD4+CD8+ double-positive T lymphocyte; IL-9; IL-9R; Melanoma; TIL