Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance

被引：300

作者：

Daley, Donnele ^{[1
]}

Mani, Vishnu R. ^{[1
]}

Mohan, Navyatha ^{[1
]}

Akkad, Neha ^{[1
]}

Ochi, Atsuo ^{[1
]}

Heindel, Daniel W. ^{[2
]}

Lee, Ki Buom ^{[1
]}

Zambirinis, Constantinos P. ^{[1
]}

Pandian, Gautam S. D. Balasubramania ^{[1
]}

Savadkar, Shivraj ^{[1
]}

Torres-Hernandez, Alejandro ^{[1
]}

Nayak, Shruti ^{[3
]}

Wang, Ding ^{[4
]}

Hundeyin, Mautin ^{[1
]}

Diskin, Brian ^{[1
]}

Aykut, Berk ^{[1
]}

Werba, Gregor ^{[1
]}

Barilla, Rocky M. ^{[1
]}

Rodriguez, Robert ^{[1
]}

Chang, Steven ^{[1
]}

Gardner, Lawrence ^{[4
]}

Mahal, Lara K. ^{[2
]}

Ueberheide, Beatrix ^{[3
]}

Miller, George ^{[1
,5
]}

机构：

[1] NYU, Dept Surg, Sch Med, SA Localio Lab, New York, NY 10016 USA

[2] NYU, Dept Chem, New York, NY USA

[3] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY USA

[4] NYU, Sch Med, Dept Med, New York, NY USA

[5] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

来源：

NATURE MEDICINE | 2017年 / 23卷 / 05期

关键词：

TUMOR-INFILTRATING LYMPHOCYTES; DUCTAL ADENOCARCINORNA; LECTIN RECEPTORS; PD-1; BLOCKADE; CELLS; INNATE; MICE; CARCINOGENESIS; CANCER; MINCLE;

D O I：

10.1038/nm.4314

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA). Dectin 1 ligation accelerated the progression of PDA in mice, whereas deletion of Clec7a-the gene encoding dectin 1-or blockade of dectin 1 downstream signaling was protective. We found that dectin 1 can ligate the lectin galectin 9 in mouse and human PDA, which results in tolerogenic macrophage programming and adaptive immune suppression. Upon disruption of the dectin 1-galectin 9 axis, CD4(+) and CD8(+) T cells, which are dispensable for PDA progression in hosts with an intact signaling axis, become reprogrammed into indispensable mediators of anti-tumor immunity. These data suggest that targeting dectin 1 signaling is an attractive strategy for developing an immunotherapy for PDA.

引用

页码：556 / +

页数：14

共 47 条

[1] Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells [J].

Anderson, Ana C. ;

Anderson, David E. ;

Bregoli, Lisa ;

Hastings, William D. ;

Kassam, Nasim ;

Lei, Charles ;

Chandwaskar, Rucha ;

Karman, Jozsef ;

Su, Ee W. ;

Hirashima, Mitsuomi ;

Bruce, Jeffrey N. ;

Kane, Lawrence P. ;

Kuchroo, Vijay K. ;

Hafler, David A. .

SCIENCE, 2007, 318 (5853) :1141-1143

[2] Etiologic links between chronic pancreatitis and pancreatic cancer [J].

AndrenSandberg, A ;

Dervenis, C ;

Lowenfels, B .

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1997, 32 (02) :97-103

[3] PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma [J].

Ansell, Stephen M. ;

Lesokhin, Alexander M. ;

Borrello, Ivan ;

Halwani, Ahmad ;

Scott, Emma C. ;

Gutierrez, Martin ;

Schuster, Stephen J. ;

Millenson, Michael M. ;

Cattry, Deepika ;

Freeman, Gordon J. ;

Rodig, Scott J. ;

Chapuy, Bjoern ;

Ligon, Azra H. ;

Zhu, Lili ;

Grosso, Joseph F. ;

Kim, Su Young ;

Timmerman, John M. ;

Shipp, Margaret A. ;

Armand, Philippe .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :311-319

[4] Tumor Galectin-1 Mediates Tumor Growth and Metastasis through Regulation of T-Cell Apoptosis [J].

Banh, Alice ;

Zhang, Jing ;

Cao, Hongbin ;

Bouley, Donna M. ;

Kwok, Shirley ;

Kong, Christina ;

Giaccia, Amato J. ;

Koong, Albert C. ;

Le, Quynh-Thu .

CANCER RESEARCH, 2011, 71 (13) :4423-4431

[5] Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer [J].

Bayne, Lauren J. ;

Beatty, Gregory L. ;

Jhala, Nirag ;

Clark, Carolyn E. ;

Rhim, Andrew D. ;

Stanger, Ben Z. ;

Vonderheide, Robert H. .

CANCER CELL, 2012, 21 (06) :822-835

[6] Dendritic Cells Promote Pancreatic Viability in Mice With Acute Pancreatitis [J].

Bedrosian, Andrea S. ;

Nguyen, Andrew H. ;

Hackman, Michael ;

Connolly, Michael K. ;

Malhotra, Ashim ;

Ibrahim, Junaid ;

Cieza-Rubio, Napoleon E. ;

Henning, Justin R. ;

Barilla, Rocky ;

Rehman, Adeel ;

Pachter, H. Leon ;

Medina-Zea, Marco V. ;

Cohen, Steven M. ;

Frey, Alan B. ;

Acehan, Devrim ;

Miller, George .

GASTROENTEROLOGY, 2011, 141 (05) :1915-U508

[7] DAMPs, PAMPs and alarmins: all we need to know about danger [J].

Bianchi, Marco E. .

JOURNAL OF LEUKOCYTE BIOLOGY, 2007, 81 (01) :1-5

[8] Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses [J].

Chiba, Shiho ;

Ikushima, Hiroaki ;

Ueki, Hiroshi ;

Yanai, Hideyuki ;

Kimura, Yoshitaka ;

Hangai, Sho ;

Nishio, Junko ;

Negishi, Hideo ;

Tamura, Tomohiko ;

Saijo, Shinobu ;

Iwakura, Yoichiro ;

Taniguchi, Tadatsugu .

ELIFE, 2014, 3 :1-20

[9] Dynamics of the immune reaction to pancreatic cancer from inception to invasion [J].

Clark, Carolyn E. ;

Hingorani, Sunil R. ;

Mick, Rosemarie ;

Combs, Chelsea ;

Tuveson, David A. ;

Vonderheide, Robert H. .

CANCER RESEARCH, 2007, 67 (19) :9518-9527

[10] Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor [J].

Connolly, Michael K. ;

Mallen-St Clair, Jon ;

Bedrosian, Andrea S. ;

Malhotra, Ashim ;

Vera, Valery ;

Ibrahim, Junaid ;

Henning, Justin ;

Pachter, H. Leon ;

Bar-Sagi, Dafna ;

Frey, Alan B. ;

Miller, George .

JOURNAL OF LEUKOCYTE BIOLOGY, 2010, 87 (04) :713-725

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