دورية أكاديمية
أعرض في EDS

Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity.

التفاصيل البيبلوغرافية
العنوان: Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity.
المؤلفون: Carmi Y; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.; Department of Pathology, The Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel., Prestwood TR; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.; Program in Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA., Spitzer MH; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA., Linde IL; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.; Program in Immunology, Stanford University School of Medicine, Stanford, California, USA., Chabon J; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Reticker-Flynn NE; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Bhattacharya N; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Zhang H; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Zhang X; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Basto PA; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Burt BM; Division of General Thoracic Surgery, Baylor College of Medicine, Houston, Texas, USA., Alonso MN; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., Engleman EG; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
المصدر: JCI insight [JCI Insight] 2016 Nov 03; Vol. 1 (18), pp. e89020. Date of Electronic Publication: 2016 Nov 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Print ISSN: 2379-3708 (Print) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
مواضيع طبية MeSH: Antigen-Antibody Complex/*immunology , Antigens, Neoplasm/*immunology , Dendritic Cells/*immunology , Lung Neoplasms/*immunology , Protein Tyrosine Phosphatase, Non-Receptor Type 6/*metabolism , Proto-Oncogene Proteins c-akt/*metabolism, Animals ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Lymphocyte Activation ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes/cytology ; Neoplasm Recurrence, Local ; Neoplasms, Experimental/immunology ; T-Lymphocytes/immunology ; Tumor Microenvironment
مستخلص: BM-derived DC (BMDC) are powerful antigen-presenting cells. When loaded with immune complexes (IC), consisting of tumor antigens bound to antitumor antibody, BMDC induce powerful antitumor immunity in mice. However, attempts to employ this strategy clinically with either tumor-associated DC (TADC) or monocyte-derived DC (MoDC) have been disappointing. To investigate the basis for this phenomenon, we compared the response of BMDC, TADC, and MoDC to tumor IgG-IC. Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells. In contrast, TADC and, surprisingly, MoDC remained inert upon contact with IC due to dysfunctional signaling following engagement of Fcγ receptors. Such dysfunction is associated with elevated levels of the Src homology region 2 domain-containing phosphatase-1 (SHP-1) and phosphatases regulating Akt activation. Indeed, concomitant inhibition of both SHP-1 and phosphatases that regulate Akt activation conferred upon TADC and MoDC the capacity to take up and process IC and induce antitumor immunity in vivo. This work identifies the molecular checkpoints that govern activation of MoDC and TADC and their capacity to elicit T cell immunity.
Competing Interests: The authors have declared that no conflict of interest exists.
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معلومات مُعتمدة: T32 GM007365 United States GM NIGMS NIH HHS; F31 CA196029 United States CA NCI NIH HHS; F31 CA189331 United States CA NCI NIH HHS; F32 CA189408 United States CA NCI NIH HHS; R01 CA196657 United States CA NCI NIH HHS; F30 CA196145 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antigen-Antibody Complex)
0 (Antigens, Neoplasm)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
EC 3.1.3.48 (Ptpn6 protein, mouse)
تواريخ الأحداث: Date Created: 20161105 Date Completed: 20181004 Latest Revision: 20190228
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC5085602
DOI: 10.1172/jci.insight.89020
PMID: 27812544
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-3708
DOI:10.1172/jci.insight.89020