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Immunosuppressive mediators impair proinflammatory innate lymphoid cell function in human malignant melanoma

Garcia-Garijo, Andrea
Salomé, Bérengère
Vanoni, Giulia
Mastelic-Gavillet, Beatris
Ianaro, Angela
Speiser, Daniel E
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Published in Cancer Immunology Research. 2020
Abstract Innate lymphoid cells (ILC) are a family of immune cells that are emerging as potent orchestrators of immune responses. In cancer, ILCs display both pro- and antitumorigenic functions depending on the nature of the tumor and the involved ILC subset. Little is known about the ILC-tumor cross-talk in human melanoma. Here, we showed that ILC1s were enriched but functionally impaired in cytokine secretion in both peripheral blood mononuclear cells and tumor-infiltrated lymph nodes of melanoma patients. These findings were confirmed in vivo in murine cutaneous melanoma. Multiple immunosuppressive mechanisms are described in the melanoma microenvironment. Among others, adenosine and kynurenines were shown to suppress antitumor immune responses. By exposing ILCs to adenosine and kynurenines, we observed a similar shift toward the ILC1 subset distribution and impairment in proinflammatory cytokine production to that of patient samples studied ex vivo Thus, we hypothesized that the immunosuppressive microenvironment of malignant melanoma might shape ILC subpopulations. Hence, we provide a rationale for the use of drugs targeting adenosine and kynurenine pathways in melanoma patients.
PMID: 32019778
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Research group Ciblage des lymphocytes sécrétant des cytokines (1015)
Swiss National Science Foundation: PZ00P3_161459
(ISO format)
ERCOLANO, Giuseppe et al. Immunosuppressive mediators impair proinflammatory innate lymphoid cell function in human malignant melanoma. In: Cancer Immunology Research, 2020. doi: 10.1158/2326-6066.CIR-19-0504

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Deposited on : 2020-03-19

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