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

Sara Trabanelli (), Mathieu F. Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M. Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A. Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N. J. McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré and Camilla Jandus ()
Additional contact information
Sara Trabanelli: University of Lausanne
Mathieu F. Chevalier: Lausanne University Hospital (CHUV)
Amaia Martinez-Usatorre: University of Lausanne
Alejandra Gomez-Cadena: University of Lausanne
Bérengère Salomé: University of Lausanne
Mariangela Lecciso: University of Bologna
Valentina Salvestrini: University of Bologna
Grégory Verdeil: University of Lausanne
Julien Racle: University of Lausanne
Cristina Papayannidis: University of Bologna
Hideaki Morita: University of Zurich
Irene Pizzitola: University of Lausanne
Camille Grandclément: University of Lausanne
Perrine Bohner: Lausanne University Hospital (CHUV)
Elena Bruni: University of Milan
Mukul Girotra: University of Lausanne
Rani Pallavi: European Institute of Oncology
Paolo Falvo: European Institute of Oncology
Elisabeth Oppliger Leibundgut: Bern University Hospital, University of Bern
Gabriela M. Baerlocher: Bern University Hospital, University of Bern
Carmelo Carlo-Stella: Humanitas Clinical and Research Center
Daniela Taurino: Humanitas Clinical and Research Center
Armando Santoro: Humanitas Clinical and Research Center
Orietta Spinelli: Ospedale Papa Giovanni XXIII
Alessandro Rambaldi: Ospedale Papa Giovanni XXIII
Emanuela Giarin: University of Padova
Giuseppe Basso: University of Padova
Cristina Tresoldi: San Raffaele Hospital
Fabio Ciceri: San Raffaele Hospital
David Gfeller: University of Lausanne
Cezmi A. Akdis: University of Zurich
Luca Mazzarella: European Institute of Oncology
Saverio Minucci: European Institute of Oncology
Pier Giuseppe Pelicci: European Institute of Oncology
Emanuela Marcenaro: University of Genoa
Andrew N. J. McKenzie: MRC Laboratory of Molecular Biology
Dominique Vanhecke: University of Lausanne
George Coukos: University of Lausanne
Domenico Mavilio: University of Milan
Antonio Curti: University of Bologna
Laurent Derré: Lausanne University Hospital (CHUV)
Camilla Jandus: University of Lausanne

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00678-2

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