Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.
Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.
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DOI：
10.1038/s41467-017-00678-2
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发表时间：
2017-09-19
影响因子：
16.6
通讯作者：
Jandus C
中科院分区：
文献类型：
--
作者：
Trabanelli S;Chevalier MF;Martinez-Usatorre A;Gomez-Cadena A;Salomé B;Lecciso M;Salvestrini V;Verdeil G;Racle J;Papayannidis C;Morita H;Pizzitola I;Grandclément C;Bohner P;Bruni E;Girotra M;Pallavi R;Falvo P;Leibundgut EO;Baerlocher GM;Carlo-Stella C;Taurino D;Santoro A;Spinelli O;Rambaldi A;Giarin E;Basso G;Tresoldi C;Ciceri F;Gfeller D;Akdis CA;Mazzarella L;Minucci S;Pelicci PG;Marcenaro E;McKenzie ANJ;Vanhecke D;Coukos G;Mavilio D;Curti A;Derré L;Jandus C
第2组先天性淋巴样细胞（ILC 2）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尚不清楚。在这里，我们表明，在急性早幼粒细胞白血病（APL），ILC 2增加和过度激活，通过CRTH 2和NKp 30与升高的肿瘤衍生的PGD 2和B7 H6，分别相互作用。ILC 2又通过IL-13分泌激活单核细胞骨髓源性抑制细胞（M-MDSC）。在用全反式维甲酸治疗APL并实现完全缓解后，PGD 2、NKp 30、ILC 2、IL-13和M-MDSC的水平恢复。类似地，通过特异性阻断PGD 2、IL-13和NKp 30来破坏这种肿瘤免疫抑制轴，部分恢复了ILC 2和M-MDSC水平，并导致存活率增加。因此，使用APL作为模型，我们发现了一个致耐受性途径，可能代表了相关的免疫抑制，治疗靶向，在各种人类肿瘤类型的机制，支持我们在前列腺癌的观察。第2组先天淋巴样细胞（ILC 2）调节炎症和过敏反应，但其在癌症免疫中的功能仍不清楚。在这里，作者表明，在急性早幼粒细胞白血病中，肿瘤激活的ILC 2分泌IL-13来诱导髓源性抑制细胞并支持肿瘤生长。
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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影响因子：
7
作者：
Cortez VS;Robinette ML;Colonna M
通讯作者：
Colonna M
DOI：
10.1126/science.aad9903
发表时间：
2016-03-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Duffin R;O'Connor RA;Crittenden S;Forster T;Yu C;Zheng X;Smyth D;Robb CT;Rossi F;Skouras C;Tang S;Richards J;Pellicoro A;Weller RB;Breyer RM;Mole DJ;Iredale JP;Anderton SM;Narumiya S;Maizels RM;Ghazal P;Howie SE;Rossi AG;Yao C
通讯作者：
Yao C
影响因子：
32.4
作者：
Diefenbach, Andreas;Colonna, Marco;Koyasu, Shigeo
通讯作者：
Koyasu, Shigeo
DOI：
10.1093/jnci/90.6.455
发表时间：
1998-03-18
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Hwang, D;Scollard, D;Levine, E
通讯作者：
Levine, E
影响因子：
20.3
作者：
Highfill, Steven L.;Rodriguez, Paulo C.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.