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Nat Commun. 2017 Sep 19;8(1):593. doi: 10.1038/s41467-017-00678-2.

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

Author information

1
Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Biopole 3-02DB61, Ch. Des Boveresses 155, CH-1066, Epalinges, Switzerland. sara.trabanelli@gmail.com.
2
Urology Research Unit, Lausanne University Hospital (CHUV), 1011, Lausanne, Switzerland.
3
Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Biopole 3-02DB61, Ch. Des Boveresses 155, CH-1066, Epalinges, Switzerland.
4
Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, 40138, Bologna, Italy.
5
Swiss Institute of Bioinformatics (SIB), 1015, Lausanne, Switzerland.
6
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7270, Davos, Switzerland.
7
Christine Kühne-Center for Allergy Research and Education, 7265, Davos, Switzerland.
8
Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20133, Milan, Italy.
9
Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089, Rozzano-Milan, Italy.
10
Department of Experimental Oncology, European Institute of Oncology, 20139, Milan, Italy.
11
Department of Hematology, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.
12
Humanitas Cancer Center, Humanitas Clinical and Research Center, 20089, Rozzano-Milan, Italy.
13
Department of Biomedical Sciences, Humanitas University, 20089, Rozzano-Milan, Italy.
14
Hematology and Bone Marrow Transplant Unit, Ospedale Papa Giovanni XXIII, 24127, Bergamo, Italy.
15
Università Statale di Milano, 20122, Milan, Italy.
16
Dipartimento per la Salute della Donna e del Bambino, Clinica di Oncoematologia Pediatrica, University of Padova, 35128, Padova, Italy.
17
Immunoematologia e Medicina Trasfusionale, Laboratorio Ematologia Molecolare, Biobanca Neoplasie Ematologiche, San Raffaele Hospital, 20132, Milano, Italy.
18
Divisione di Ricerca di Medicina Rigenerativa, Terapia Cellulare e Genica IRCCS, San Raffaele Hospital, 20132, Milano, Italy.
19
Division of Innovative Therapies, European Institute of Oncology, 20141, Milan, Italy.
20
Department of Experimental Medicine (DI.ME.S.)-Section of Histology, and Center of Excellent of Biomedical Research (CEBR), University of Genoa, 16132, Genoa, Italy.
21
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
22
Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Biopole 3-02DB61, Ch. Des Boveresses 155, CH-1066, Epalinges, Switzerland. camilla.jandus@chuv.ch.

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.

PMID:
28928446
PMCID:
PMC5605498
DOI:
10.1038/s41467-017-00678-2
[Indexed for MEDLINE]
Free PMC Article

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