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

被引：189

作者：

Trabanelli, Sara ^{[1
]}

Chevalier, Mathieu F. ^{[2
]}

Martinez-Usatorre, Amaia ^{[1
]}

Gomez-Cadena, Alejandra ^{[1
]}

Salome, Berengere ^{[1
]}

Lecciso, Mariangela ^{[3
]}

Salvestrini, Valentina ^{[3
]}

Verdeil, Gregory ^{[1
]}

Racle, Julien ^{[1
,4
]}

Papayannidis, Cristina ^{[3
]}

Morita, Hideaki ^{[5
,6
]}

Pizzitola, Irene ^{[1
]}

Grandclement, Camille ^{[1
]}

Bohner, Perrine ^{[2
]}

Bruni, Elena ^{[7
,8
]}

Girotra, Mukul ^{[1
]}

Pallavi, Rani ^{[9
]}

Falvo, Paolo ^{[9
]}

Leibundgut, Elisabeth Oppliger ^{[10
]}

Baerlocher, Gabriela M. ^{[10
]}

Carlo-Stella, Carmelo ^{[11
,12
]}

Taurino, Daniela ^{[11
,12
]}

Santoro, Armando ^{[11
,12
]}

Spinelli, Orietta ^{[13
]}

Rambaldi, Alessandro ^{[13
,14
]}

Giarin, Emanuela ^{[15
]}

Basso, Giuseppe ^{[15
]}

Tresoldi, Cristina ^{[16
]}

Ciceri, Fabio ^{[17
]}

Gfeller, David ^{[1
,4
]}

Akdis, Cezmi A. ^{[5
]}

Mazzarella, Luca ^{[9
,18
]}

Minucci, Saverio ^{[9
]}

Pelicci, Pier Giuseppe ^{[9
]}

Marcenaro, Emanuela ^{[19
,20
]}

McKenzie, Andrew N. J. ^{[21
]}

Vanhecke, Dominique ^{[1
]}

Coukos, George ^{[1
]}

Mavilio, Domenico ^{[7
,8
]}

Curti, Antonio ^{[3
]}

Derre, Laurent ^{[2
]}

Jandus, Camilla ^{[1
]}

机构：

[1] Univ Lausanne, Dept Fundamental Oncol, Ludwig Inst Canc Res, Biopole 3-02DB61,Ch Boveresses 155, CH-1066 Epalinges, Switzerland

[2] Lausanne Univ Hosp CHUV, Urol Res Unit, CH-1011 Lausanne, Switzerland

[3] Univ Bologna, Inst Hematol Seragnoli, Dept Specialist Diagnost & Expt Med, I-40138 Bologna, Italy

[4] SIB, CH-1015 Lausanne, Switzerland

[5] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, CH-7270 Davos, Switzerland

[6] Christine Kuhne Ctr Allergy Res & Educ, CH-7265 Davos, Switzerland

[7] Univ Milan, Dept Med Biotechnol & Translat Med, I-20133 Milan, Italy

[8] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, I-20089 Rozzano Milan, Italy

[9] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy

[10] Univ Bern, Bern Univ Hosp, Dept Hematol, CH-3010 Bern, Switzerland

[11] Humanitas Clin & Res Ctr, Humanitas Canc Ctr, I-20089 Rozzano Milan, Italy

[12] Humanitas Univ, Dept Biomed Sci, I-20089 Rozzano Milan, Italy

[13] Osped Papa Giovanni XXIII, Hematol & Bone Marrow Transplant Unit, I-24127 Bergamo, Italy

[14] Univ Milan, I-20122 Milan, Italy

[15] Univ Padua, Clin Oncoematol Pediat, Dipartimento Salute Donna & Bambino, I-35128 Padua, Italy

[16] Osped San Raffaele, Biobanca Neoplasie Ematol, Lab Ematol Mol, Immunoematol & Med Trasfus, I-20132 Milan, Italy

[17] Osped San Raffaele, IRCCS, Div Ric Med Rigenerat Terapia Cellulare & Genica, I-20132 Milan, Italy

[18] European Inst Oncol, Div Innovat Therapies, I-20141 Milan, Italy

[19] Univ Genoa, Sect Histol, Dept Expt Med DIMES, I-16132 Genoa, Italy

[20] Univ Genoa, CEBR, I-16132 Genoa, Italy

[21] MRC Lab Mol Biol, Cambridge CB2 0QH, England

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

瑞士国家科学基金会;

关键词：

INNATE LYMPHOID-CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; T-CELLS; SUPPRESSOR-CELLS; BREAST-CANCER; EXPRESSION; IMMUNITY; GROWTH; INFLAMMATION; CYCLOOXYGENASE-2;

D O I：

10.1038/s41467-017-00678-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 54 条

[1] Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure
Ablain, Julien
Rice, Kim
Soilihi, Hassane
de Reynies, Aurelien
Minucci, Saverio
de The, Hugues
[J]. NATURE MEDICINE, 2014, 20 (02) : 167 - 174
[2] Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese diabetic/severe combined immunodeficient mice
Ailles, LE
Gerhard, B
Kawagoe, M
Hogge, DE
[J]. BLOOD, 1999, 94 (05) : 1761 - 1772
[3] The role of ILC2 in pathology of type 2 inflammatory diseases
Bernink, Jochem H.
Germar, Kristine
Spits, Hergen
[J]. CURRENT OPINION IN IMMUNOLOGY, 2014, 31 : 115 - 120
[4] Polarization of ILC2s in Peripheral Blood Might Contribute to Immunosuppressive Microenvironment in Patients with Gastric Cancer
Bie, Qingli
Zhang, Pan
Su, Zhaoliang
Zheng, Dong
Ying, Xinyu
Wu, Yumin
Yang, Huijian
Chen, Deyu
Wang, Shengjun
Xu, Huaxi
[J]. JOURNAL OF IMMUNOLOGY RESEARCH, 2014, 2014
[5] Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Bronte, Vincenzo
Brandau, Sven
Chen, Shu-Hsia
Colombo, Mario P.
Frey, Alan B.
Greten, Tim F.
Mandruzzato, Susanna
Murray, Peter J.
Ochoa, Augusto
Ostrand-Rosenberg, Suzanne
Rodriguez, Paulo C.
Sica, Antonio
Umansky, Viktor
Vonderheide, Robert H.
Gabrilovich, Dmitry I.
[J]. NATURE COMMUNICATIONS, 2016, 7
[6] A PMLRAR alpha transgene initiates murine acute promyelocytic leukemia
Brown, D
Kogan, S
Lagasse, E
Weissman, I
Alcalay, M
Pelicci, PG
Atwater, S
Bishop, JM
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) : 2551 - 2556
[7] NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures
Carrega, Paolo
Loiacono, Fabrizio
Di Carlo, Emma
Scaramuccia, Angelo
Mora, Marco
Conte, Romana
Benelli, Roberto
Spaggiari, Grazia Maria
Cantoni, Claudia
Campana, Stefania
Bonaccorsi, Irene
Morandi, Barbara
Truini, Mauro
Mingari, Maria Cristina
Moretta, Lorenzo
Ferlazzo, Guido
[J]. NATURE COMMUNICATIONS, 2015, 6
[8] Celis JE, 1996, CANCER RES, V56, P4782
[9] Innate lymphoid cells: new insights into function and development
Cortez, Victor S.
Robinette, Michelle L.
Colonna, Marco
[J]. CURRENT OPINION IN IMMUNOLOGY, 2015, 32 : 71 - 77
[10] Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival
Di Lullo, Giulia
Marcatti, Magda
Heltai, Silvia
Brunetto, Emanuela
Tresoldi, Cristina
Bondanza, Attilio
Bonini, Chiara
Ponzoni, Maurilio
Tonon, Giovanni
Ciceri, Fabio
Bordignon, Claudio
Protti, Maria Pia
[J]. ONCOIMMUNOLOGY, 2015, 4 (05):

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