دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.
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
الوصف
تدمد:1546-170X
DOI:10.1038/nm.4314