Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.

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State: Public
Version: author
Serval ID
serval:BIB_40D92F523196
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.
Journal
Nature communications
Author(s)
Trabanelli S., Chevalier M.F., Martinez-Usatorre A., Gomez-Cadena A., Salomé B., Lecciso M., Salvestrini V., Verdeil G., Racle J., Papayannidis C., Morita H., Pizzitola I., Grandclément C., Bohner P., Bruni E., Girotra M., Pallavi R., Falvo P., Leibundgut E.O., Baerlocher G.M., Carlo-Stella C., Taurino D., Santoro A., Spinelli O., Rambaldi A., Giarin E., Basso G., Tresoldi C., Ciceri F., Gfeller D., Akdis C.A., Mazzarella L., Minucci S., Pelicci P.G., Marcenaro E., McKenzie ANJ, Vanhecke D., Coukos G., Mavilio D., Curti A., Derré L., Jandus C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
19/09/2017
Peer-reviewed
Oui
Volume
8
Number
1
Pages
593
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.

Keywords
A549 Cells, Animals, Antineoplastic Agents/therapeutic use, B7 Antigens/immunology, B7 Antigens/metabolism, Cell Line, Tumor, Disease Models, Animal, HL-60 Cells, Hep G2 Cells, Humans, Immunity, Innate/immunology, Interleukin-13/immunology, Interleukin-13/secretion, Leukemia, Promyelocytic, Acute/drug therapy, Leukemia, Promyelocytic, Acute/immunology, Leukemia, Promyelocytic, Acute/metabolism, Lymphocytes/immunology, Lymphocytes/metabolism, Mice, Inbred C57BL, Myeloid-Derived Suppressor Cells/immunology, Myeloid-Derived Suppressor Cells/metabolism, Natural Cytotoxicity Triggering Receptor 3/immunology, Natural Cytotoxicity Triggering Receptor 3/metabolism, Prostaglandin D2/immunology, Prostaglandin D2/metabolism, Protein Binding, Tretinoin/therapeutic use
Pubmed
Web of science
Open Access
Yes
Create date
21/09/2017 13:49
Last modification date
25/05/2020 15:31
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