دورية أكاديمية
أعرض في EDS

Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.

التفاصيل البيبلوغرافية
العنوان: Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.
المؤلفون: Li X; Central Laboratory, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, P. R. China., Su N; Central Laboratory, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, P. R. China., Yu H; School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, 116024, P. R. China. 576609286@qq.com., Li X; Department of Pathology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, P. R. China. lixiaoyan@cancerhosp-ln-cmu.com., Sun SL; Central Laboratory, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, P. R. China. sunshulan@cancerhosp-ln-cmu.com.
المصدر: Cell communication and signaling : CCS [Cell Commun Signal] 2024 Jul 05; Vol. 22 (1), pp. 352. Date of Electronic Publication: 2024 Jul 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2003-
مواضيع طبية MeSH: Triple Negative Breast Neoplasms*/pathology , Triple Negative Breast Neoplasms*/immunology , Immunogenic Cell Death*/drug effects , Membrane Proteins*/metabolism , Membrane Proteins*/genetics, Animals ; Humans ; Female ; Mice ; Cell Line, Tumor ; Mice, Inbred BALB C ; Dendritic Cells/immunology ; Dendritic Cells/drug effects ; Dendritic Cells/metabolism
مستخلص: Background: In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism.
Methods: We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1.
Results: HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions.
Conclusions: Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 82202861 National Natural Science Foundation of China; LD202209/LD202024 /LD202115 Fundamental Research Funds for the Central University; 2023-MS-058 Science and Technology Foundation of Liaoning Province; Y-tongshu2021/ms-0270 Beijing Xisike Clinical Oncology Research Foundation; 2022-YQ-08 to SL. S Outstanding Youth Foundation of Liaoning; 2021-YGJC-22 Science and Technology Plan Project of Liaoning
فهرسة مساهمة: Keywords: Anti-tumor immunity; HN-1; Host defense peptide; Immunogenic cell death; STING; Triple-negative breast cancer
المشرفين على المادة: 0 (Membrane Proteins)
0 (STING1 protein, human)
تواريخ الأحداث: Date Created: 20240705 Date Completed: 20240705 Latest Revision: 20240708
رمز التحديث: 20240708
مُعرف محوري في PubMed: PMC11225514
DOI: 10.1186/s12964-024-01731-6
PMID: 38970078
قاعدة البيانات: MEDLINE
الوصف
تدمد:1478-811X
DOI:10.1186/s12964-024-01731-6