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

by Verdeil, Grégory , Lecciso, Mariangela , Leibundgut, Elisabeth Oppliger , Gomez-Cadena, Alejandra , Jandus, Camilla , Falvo, Paolo , Ciceri, Fabio , Salomé, Bérengère , Carlo-Stella, Carmelo , Derré, Laurent , Spinelli, Orietta , Martinez-Usatorre, Amaia , Taurino, Daniela , Pelicci, Pier Giuseppe , Akdis, Cezmi A. , Curti, Antonio , Baerlocher, Gabriela M. , Minucci, Saverio , Morita, Hideaki , Bruni, Elena , Vanhecke, Dominique , Tresoldi, Cristina , Papayannidis, Cristina , Giarin, Emanuela , Mazzarella, Luca , Chevalier, Mathieu F. , Basso, Giuseppe , Coukos, George , Salvestrini, Valentina , Gfeller, David , Racle, Julien , Santoro, Armando , Rambaldi, Alessandro , Mavilio, Domenico , Marcenaro, Emanuela , McKenzie, Andrew N. J. , Pizzitola, Irene , Girotra, Mukul , Trabanelli, Sara , Bohner, Perrine , Grandclément, Camille , Pallavi, Rani

in 631/250/127 / 631/250/2161 / 631/250/2504/2506 / 631/67/327 / A549 Cells / Allergies / Animals / Antineoplastic Agents - therapeutic use / Atopic dermatitis / B7 Antigens - immunology / B7 Antigens - metabolism / Cancer / Cell Line, Tumor / Dermatitis / Disease Models, Animal / Disruption / Hep G2 Cells / HL-60 Cells / Humanities and Social Sciences / Humans / Immunity / Immunity, Innate - immunology / Immunology / Immunosuppression / Inflammation / Interleukin 13 / Interleukin-13 - immunology / Interleukin-13 - metabolism / Leukemia / Leukemia, Promyelocytic, Acute - drug therapy / Leukemia, Promyelocytic, Acute - immunology / Leukemia, Promyelocytic, Acute - metabolism / Life Sciences / Lymphocytes - immunology / Lymphocytes - metabolism / Lymphoid cells / Mice, Inbred C57BL / Monocytes / multidisciplinary / Myeloid-Derived Suppressor Cells - immunology / Myeloid-Derived Suppressor Cells - metabolism / Natural Cytotoxicity Triggering Receptor 3 - immunology / Natural Cytotoxicity Triggering Receptor 3 - metabolism / Polyposis / Prostaglandin D2 - immunology / Prostaglandin D2 - metabolism / Prostate cancer / Protein Binding / Remission / Retinoic acid / Science / Science (multidisciplinary) / Suppressor cells / Tretinoin / Tretinoin - therapeutic use / Tumors

2017

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

2017

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

2017

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Journal Article

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

Verdeil, Grégory,

Lecciso, Mariangela,

Leibundgut, Elisabeth Oppliger,

Gomez-Cadena, Alejandra,

Jandus, Camilla,

Falvo, Paolo,

Ciceri, Fabio,

Salomé, Bérengère,

Carlo-Stella, Carmelo,

Derré, Laurent,

Spinelli, Orietta,

Martinez-Usatorre, Amaia,

Taurino, Daniela,

Pelicci, Pier Giuseppe,

Akdis, Cezmi A.,

Curti, Antonio,

Baerlocher, Gabriela M.,

Minucci, Saverio,

Morita, Hideaki,

Bruni, Elena,

Vanhecke, Dominique,

Tresoldi, Cristina,

Papayannidis, Cristina,

Giarin, Emanuela,

Mazzarella, Luca,

Chevalier, Mathieu F.,

Basso, Giuseppe,

Coukos, George,

Salvestrini, Valentina,

Gfeller, David,

Racle, Julien,

Santoro, Armando,

Rambaldi, Alessandro,

Mavilio, Domenico,

Marcenaro, Emanuela,

McKenzie, Andrew N. J.,

Pizzitola, Irene,

Girotra, Mukul,

Trabanelli, Sara,

Bohner, Perrine,

Grandclément, Camille,

Pallavi, Rani

2017

Overview

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.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ Animals