دورية أكاديمية
Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.
العنوان: | Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. |
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المؤلفون: | Daley D; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Mani VR; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Mohan N; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Akkad N; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Ochi A; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Heindel DW; Department of Chemistry, New York University, New York, New York, USA., Lee KB; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Zambirinis CP; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Pandian GSB; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Savadkar S; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Torres-Hernandez A; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Nayak S; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA., Wang D; Department of Medicine, New York University School of Medicine, New York, New York, USA., Hundeyin M; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Diskin B; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Aykut B; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Werba G; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Barilla RM; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Rodriguez R; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Chang S; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA., Gardner L; Department of Medicine, New York University School of Medicine, New York, New York, USA., Mahal LK; Department of Chemistry, New York University, New York, New York, USA., Ueberheide B; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA., Miller G; S.A. Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York, USA.; Department of Cell Biology, New York University School of Medicine, New York, New York, USA. |
المصدر: | Nature medicine [Nat Med] 2017 May; Vol. 23 (5), pp. 556-567. Date of Electronic Publication: 2017 Apr 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
مواضيع طبية MeSH: | Carcinoma, Pancreatic Ductal/*genetics , Galectins/*metabolism , Lectins, C-Type/*genetics , Pancreatic Neoplasms/*genetics , Tumor Escape/*genetics, Animals ; Blotting, Western ; Carcinogenesis/genetics ; Carcinoma, Pancreatic Ductal/immunology ; Carcinoma, Pancreatic Ductal/metabolism ; Epithelial Cells/metabolism ; Flow Cytometry ; Gene Knockdown Techniques ; Humans ; Immune Tolerance/genetics ; Immunohistochemistry ; Immunoprecipitation ; Lectins, C-Type/immunology ; Lectins, C-Type/metabolism ; Mass Spectrometry ; Mice ; Mice, Knockout ; Pancreatic Ducts/cytology ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/metabolism ; Syk Kinase/genetics ; Syk Kinase/metabolism ; Tumor Escape/immunology |
مستخلص: | 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. |
التعليقات: | Erratum in: Nat Med. 2021 Dec;27(12):2247-2248. doi: 10.1038/s41591-021-01428-0. (PMID: 34845391) |
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معلومات مُعتمدة: | UL1 TR001445 United States TR NCATS NIH HHS; P30 CA016087 United States CA NCI NIH HHS; R01 CA168611 United States CA NCI NIH HHS; T32 CA193111 United States CA NCI NIH HHS; R21 CA155649 United States CA NCI NIH HHS; R01 CA206105 United States CA NCI NIH HHS; K08 DK085278 United States DK NIDDK NIH HHS; UL1 TR000038 United States TR NCATS NIH HHS |
المشرفين على المادة: | 0 (Galectins) 0 (LGALS9 protein, human) 0 (Lectins, C-Type) 0 (dectin 1) 0 (galectin 9, mouse) EC 2.7.10.2 (Syk Kinase) |
تواريخ الأحداث: | Date Created: 20170411 Date Completed: 20170814 Latest Revision: 20240610 |
رمز التحديث: | 20240610 |
مُعرف محوري في PubMed: | PMC5419876 |
DOI: | 10.1038/nm.4314 |
PMID: | 28394331 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1546-170X |
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DOI: | 10.1038/nm.4314 |