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, Leibundgut Elisabeth Oppliger, Baerlocher Gabriela M, Carlo-Stella Carmelo, Taurino Daniela, Santoro Armando, Spinelli Orietta, Rambaldi Alessandro, Giarin Emanuela, Basso Giuseppe, Tresoldi Cristina, Ciceri Fabio, Gfeller David, Akdis Cezmi A, Mazzarella Luca, Minucci Saverio, Pelicci Pier Giuseppe, Marcenaro Emanuela, McKenzie Andrew N J, Vanhecke Dominique, Coukos George, Mavilio Domenico, Curti Antonio, Derré Laurent, Jandus Camilla
Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Biopole 3-02DB61, Ch. Des Boveresses 155, CH-1066, Epalinges, Switzerland.
Urology Research Unit, Lausanne University Hospital (CHUV), 1011, Lausanne, Switzerland.
Nat Commun. 2017 Sep 19;8(1):593. doi: 10.1038/s41467-017-00678-2.
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.
第2组固有淋巴细胞（ILC2s）参与人类疾病，如过敏、特应性皮炎和鼻息肉病，但其在人类癌症中的功能仍不清楚。在此我们表明，在急性早幼粒细胞白血病（APL）中，ILC2s数量增加且过度活化，分别是通过CRTH2与升高的肿瘤源性前列腺素D2（PGD2）相互作用，以及NKp30与升高的B7H6相互作用实现的。反过来，ILC2s通过分泌白细胞介素13（IL-13）激活单核细胞来源的髓系抑制细胞（M-MDSCs）。用全反式维甲酸治疗APL并实现完全缓解后，PGD2、NKp30、ILC2s、IL-13和M-MDSCs的水平恢复正常。同样，通过特异性阻断PGD2、IL-13和NKp30来破坏这条肿瘤免疫抑制轴，可部分恢复ILC2和M-MDSC的水平，并提高生存率。因此，以APL为模型，我们发现了一条促耐受性途径，该途径可能代表了一种相关的免疫抑制机制，可作为治疗靶点作用于各种人类肿瘤类型，我们在前列腺癌中的观察结果也支持了这一点。第2组固有淋巴细胞（ILC2s）调节炎症和过敏反应，但其在癌症免疫中的功能仍不清楚。本文作者表明，在急性早幼粒细胞白血病中，肿瘤激活的ILC2s分泌IL-13以诱导髓系抑制细胞并支持肿瘤生长。
