دورية أكاديمية
أعرض في EDS

SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses.

التفاصيل البيبلوغرافية
العنوان: SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses.
المؤلفون: Burton AM; Department of Biology, University of Portland, Portland, OR, United States., Ligman BR; Department of Biology, University of Portland, Portland, OR, United States., Kearney CA; Department of Biology, University of Portland, Portland, OR, United States., Murray SE; Department of Biology, University of Portland, Portland, OR, United States; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, United States. Electronic address: murrays@up.edu.
المصدر: Cellular immunology [Cell Immunol] 2023 Feb; Vol. 384, pp. 104674. Date of Electronic Publication: 2023 Jan 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 1246405 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2163 (Electronic) Linking ISSN: 00088749 NLM ISO Abbreviation: Cell Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: <2000- > : Amsterdam : Elsevier
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Caspases*/pharmacology , Caspases*/therapeutic use , Neoplasms*/drug therapy, Humans ; Inhibitor of Apoptosis Proteins/metabolism ; Inhibitor of Apoptosis Proteins/pharmacology ; Inhibitor of Apoptosis Proteins/therapeutic use ; Cytokines ; Apoptosis ; Mitochondria/metabolism ; Cell Proliferation ; Mitochondrial Proteins/metabolism ; Cell Line, Tumor
مستخلص: Second mitochondria-derived activator of caspases (SMAC) mimetics are small molecule drugs that mimic the activity of the endogenous SMAC protein. SMAC and SMAC mimetics antagonize inhibitors of apoptosis proteins (IAPs), thereby sensitizing cells to apoptosis. As such, SMAC mimetics are being tested in numerous clinical trials for cancer. In addition to their direct anti-cancer effect, it has been suggested that SMAC mimetics may activate T cells, thereby promoting anti-tumor immunity. Here, we tested the effect of three clinically relevant SMAC mimetics on activation of primary human T cells. As previously reported, SMAC mimetics killed tumor cells and activated non-canonical NF-κB in T cells at clinically relevant doses. Surprisingly, none of the SMAC mimetics augmented T cell responses. Rather, SMAC mimetics impaired T cell proliferation and decreased the proportion of IFNγ/TNFα double-producing T cells. These results question the assumption that SMAC mimetics are likely to boost anti-tumor immunity in cancer patients.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
التعليقات: Comment in: Cell Immunol. 2024 Jan-Feb;395-396:104772. (PMID: 37996259)
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معلومات مُعتمدة: R15 CA267840 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Cancer; Cytokine; Human; IAP; SMAC mimetic; T cells
المشرفين على المادة: EC 3.4.22.- (Caspases)
0 (Inhibitor of Apoptosis Proteins)
0 (Cytokines)
0 (Mitochondrial Proteins)
تواريخ الأحداث: Date Created: 20230127 Date Completed: 20230207 Latest Revision: 20240320
رمز التحديث: 20240321
مُعرف محوري في PubMed: PMC10319349
DOI: 10.1016/j.cellimm.2023.104674
PMID: 36706656
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2163
DOI:10.1016/j.cellimm.2023.104674