RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis

被引：188

作者：

Strauss, Laura ^{[1
]}

Sangaletti, Sabina ^{[4
]}

Consonni, Francesca Maria ^{[2
]}

Szebeni, Gabor ^{[1
]}

Morlacchi, Sara ^{[1
]}

Totaro, Maria Grazia ^{[1
]}

Porta, Chiara ^{[2
]}

Anselmo, Achille ^{[1
]}

Tartari, Silvia ^{[1
]}

Doni, Andrea ^{[1
]}

Zitelli, Francesco ^{[2
]}

Tripodo, Claudio ^{[3
]}

Colombo, Mario P. ^{[4
]}

Sica, Antonio ^{[1
,2
]}

机构：

[1] Humanitas Clin & Res Ctr, Dept Inflammat & Immunol, I-20089 Milan, Italy

[2] Univ Piemonte Orientale Amedeo Avogadro, Dept Pharmaceut Sci, I-28100 Novara, Italy

[3] Univ Palermo, Dept Hlth Sci, Tumor Immunol Unit, I-90127 Palermo, Italy

[4] Fdn IRCCS, Ist Nazl Tumori, Expt Oncol, I-20133 Milan, Italy

来源：

CANCER CELL | 2015年 / 28卷 / 02期

关键词：

COLONY-STIMULATING FACTOR; KAPPA-B ACTIVATION; SUPPRESSOR-CELLS; T-CELLS; NUCLEAR RECEPTORS; CUTTING EDGE; BEARING MICE; C/EBP-BETA; GAMMA-T; GM-CSF;

D O I：

10.1016/j.ccell.2015.07.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/ROR gamma) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and BcI3) and promoting positive (C/EBID beta) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from apoptosis, mediating TAM differentiation and M2 polarization, and limiting tumor infiltration by mature neutrophils. Accordingly, ablation of RORC1 in the hematopoietic compartment prevented cancer-driven myelopoiesis, resulting in inhibition of tumor growth and metastasis.

引用

页码：253 / 269

页数：17

共 52 条

[1]

Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBPβ-deficient hematopoietic cells [J].

Akagi, Tadayuki ;

Saitoh, Takayuki ;

O'Kelly, James ;

Akira, Shizuo ;

Gombart, Adrian F. ;

Koeffler, H. Phillip .

BLOOD, 2008, 111 (06) :2999-3004

[2]

Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche [J].

Chow, Andrew ;

Lucas, Daniel ;

Hidalgo, Andres ;

Mendez-Ferrer, Simon ;

Hashimoto, Daigo ;

Scheiermann, Christoph ;

Battista, Michela ;

Leboeuf, Marylene ;

Prophete, Colette ;

van Rooijen, Nico ;

Tanaka, Masato ;

Merad, Miriam ;

Frenette, Paul S. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (02) :261-271

[3]

IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis [J].

Coffelt, Seth B. ;

Kersten, Kelly ;

Doornebal, Chris W. ;

Weiden, Jorieke ;

Vrijland, Kim ;

Hau, Cheei-Sing ;

Verstegen, Niels J. M. ;

Ciampricotti, Metamia ;

Hawinkels, Lukas J. A. C. ;

Jonkers, Jos ;

de Visser, Karin E. .

NATURE, 2015, 522 (7556) :345-+

[4]

SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis [J].

Croker, BA ;

Metcalf, D ;

Robb, L ;

Wei, W ;

Mifsud, S ;

DiRago, L ;

Cluse, LA ;

Sutherland, KD ;

Hartley, L ;

Williams, E ;

Zhang, JG ;

Hilton, DJ ;

Nicola, NA ;

Alexander, WS ;

Roberts, AW .

IMMUNITY, 2004, 20 (02) :153-165

[5]

Transcriptional control of granulocyte and monocyte development [J].

Friedman, A. D. .

ONCOGENE, 2007, 26 (47) :6816-6828

[6]

Coordinated regulation of myeloid cells by tumours [J].

Gabrilovich, Dmitry I. ;

Ostrand-Rosenberg, Suzanne ;

Bronte, Vincenzo .

NATURE REVIEWS IMMUNOLOGY, 2012, 12 (04) :253-268

[7]

Regulation of steady-state neutrophil homeostasis by macrophages [J].

Gordy, Claire ;

Pua, Heather ;

Sempowski, Gregory D. ;

He, You-Wen .

BLOOD, 2011, 117 (02) :618-629

[8]

Cutting Edge: Identification of a Motile IL-17-Producing γδ T Cell Population in the Dermis [J].

Gray, Elizabeth E. ;

Suzuki, Kazuhiro ;

Cyster, Jason G. .

JOURNAL OF IMMUNOLOGY, 2011, 186 (11) :6091-6095

[9]

Role of C5A in inflammatory responses [J].

Guo, RF ;

Ward, PA .

ANNUAL REVIEW OF IMMUNOLOGY, 2005, 23 :821-852

[10]

INDUCTION OF MAMMARY-TUMORS BY EXPRESSION OF POLYOMAVIRUS MIDDLE T-ONCOGENE - A TRANSGENIC MOUSE MODEL FOR METASTATIC DISEASE [J].

GUY, CT ;

CARDIFF, RD ;

MULLER, WJ .

MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (03) :954-961

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