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.
Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis / S. Trabanelli, M.F. Chevalier, A. Martinez Usatorre, A. Gomez Cadena, B. Salomã©, M. Lecciso, V. Salvestrini, G. Verdeil, J. Racle, C. Papayannidis, H. Morita, I. Pizzitola, C. Grandclã©ment, P. Bohner, E. Bruni, M. Girotra, R. Pallavi, P. Falvo, E.O. Leibundgut, G.M. Baerlocher, C. Carlo-Stella, D. Taurino, A. Santoro, O. Spinelli, A. Rambaldi, E. Giarin, G. Basso, C. Tresoldi, F. Ciceri, D. Gfeller, C.A. Akdis, L. Mazzarella, S. Minucci, P.G. Pelicci, E. Marcenaro, A.N..J. Mckenzie, D. Vanhecke, G. Coukos, D. Mavilio, A. Curti, L. Derrã©, C. Jandus. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:1(2017 Sep 19). [10.1038/s41467-017-00678-2]
Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis
E. Bruni;P. Falvo;C. Carlo-Stella;D. Taurino;A. Rambaldi;C. Tresoldi;L. Mazzarella;S. Minucci;P.G. Pelicci;D. Mavilio;
2017
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.
| File | Dimensione | Formato | |
|---|---|---|---|
|
ZZZI:Trabanelli S. et al.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Dimensione
1.3 MB
Formato
Adobe PDF
|
1.3 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
