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

Chevalier, Mathieu F
Martinez-Usatorre, Amaia
Salomé, Bérengère
Lecciso, Mariangela
Salvestrini, Valentina
Verdeil, Grégory
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Published in Nature communications. 2017, vol. 8, no. 1, 593
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 CellsAnimalsAntineoplastic Agents/therapeutic useB7 Antigens/immunology/metabolismCell LineTumorDisease ModelsAnimalHL-60 CellsHep G2 CellsHumansImmunityInnate/immunologyInterleukin-13/immunology/metabolismLeukemiaPromyelocyticAcute/drug therapy/immunology/metabolismLymphocytes/immunology/metabolismMiceInbred C57BLMyeloid-Derived Suppressor Cells/immunology/metabolismNatural Cytotoxicity Triggering Receptor 3/immunology/metabolismProstaglandin D2/immunology/metabolismProtein BindingTretinoin/therapeutic use
PMID: 28928446
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Research group Ciblage des lymphocytes sécrétant des cytokines (1015)
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TRABANELLI, Sara et al. Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. In: Nature Communications, 2017, vol. 8, n° 1, p. 593. doi: 10.1038/s41467-017-00678-2

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Deposited on : 2020-03-17

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