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

Trabanelli, Sara; Chevalier, Mathieu F; Martinez-Usatorre, Amaia; Gomez-Cadena, Alejandra; Salomé, Bérengère; Lecciso, Mariangela; Salvestrini, Valentina; Verdeil, Grégory; Racle, Julien; Papayannidis, Cristina; Morita, Hideaki; Pizzitola, Irene; Grandclément, Camille; Bohner, Perrine; Bruni, Elena; Girotra, Mukul; Pallavi, Rani; Falvo, Paolo; Oppliger Leibundgut, Elisabeth; Baerlocher, Gabriela M.; ... (2017). Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nature communications, 8(1), p. 593. Nature Publishing Group 10.1038/s41467-017-00678-2

[img]
Preview
Text
GMB EO_Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology

UniBE Contributor:

Oppliger Leibundgut, Elisabeth; Baerlocher, Gabriela M. and Derré, Laurent

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Katrin Kölliker-Schütz

Date Deposited:

11 Dec 2017 08:41

Last Modified:

17 Dec 2017 02:16

Publisher DOI:

10.1038/s41467-017-00678-2

PubMed ID:

28928446

BORIS DOI:

10.7892/boris.106228

URI:

https://boris.unibe.ch/id/eprint/106228

Actions (login required)

Edit item Edit item
Provide Feedback