Exosomal ITGB2 Mediates Immune Evasion in Triple-Negative Breast Cancer by Suppressing Dendritic Cell Activation via TLR4.

IF 1.6 4区医学 Q4 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

Iranian Journal of Public Health Pub Date : 2025-06-01 DOI:10.18502/ijph.v54i6.18903

Puerkaiti Paierhati, Binlin Ma, Muzhapaer Abudukeremu

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Abstract

Background: This study investigates the role of exosomal integrin beta-2 (ITGB2) from triple-negative breast cancer (TNBC) cells in modulating immune responses, with a focus on its interaction with Toll-like receptor 4 (TLR4) in dendritic cells (DCs). This study aimed to understand how ITGB2 contributes to the immunosuppressive tumor microenvironment in TNBC.

Methods: ITGB2 expression in TNBC tissues and cell lines was analyzed using qPCR and Western blot at the Affiliated Cancer Hospital of Xinjiang Medical University between 2013 and 2015. Knockdown and overexpression models of ITGB2 were established in MDA-MB-231 cells to explore their effects on TLR4 expression in DCs. Exosomes were isolated from these cells, and DCs were co-cultured with exosomes to measure TLR4 expression and cytokine secretion using flow cytometry and ELISA.

Results: ITGB2 was overexpressed in TNBC tissues, correlating with poor prognosis. Exosomal ITGB2 from TNBC cells suppressed TLR4 expression in DCs, leading to impaired DC maturation and reduced cytokine secretion, thus promoting an immunosuppressive microenvironment.

Conclusion: Targeting the ITGB2-TLR4 axis could enhance anti-tumor immunity in TNBC. ITGB2 holds potential as a biomarker and therapeutic target, suggesting that inhibition of exosomal ITGB2 or restoration of DC function may improve therapeutic outcomes in TNBC.

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外泌体ITGB2通过TLR4抑制树突状细胞激活介导三阴性乳腺癌的免疫逃避

背景：本研究探讨了三阴性乳腺癌（TNBC）细胞外泌体整合素β -2 （ITGB2）在调节免疫应答中的作用，重点研究了其与树突状细胞（dc）中toll样受体4 （TLR4）的相互作用。本研究旨在了解ITGB2在TNBC中如何参与免疫抑制肿瘤微环境。方法：采用qPCR和Western blot方法分析新疆医科大学附属肿瘤医院2013 - 2015年TNBC组织和细胞系中ITGB2的表达。在MDA-MB-231细胞中建立ITGB2敲低和过表达模型，探讨其对dc中TLR4表达的影响。从这些细胞中分离外泌体，将dc与外泌体共培养，利用流式细胞术和ELISA检测TLR4的表达和细胞因子的分泌。结果：ITGB2在TNBC组织中过表达，与预后不良相关。来自TNBC细胞的外泌体ITGB2抑制DC中TLR4的表达，导致DC成熟受损和细胞因子分泌减少，从而促进免疫抑制微环境。结论：靶向ITGB2-TLR4轴可增强TNBC的抗肿瘤免疫。ITGB2具有作为生物标志物和治疗靶点的潜力，表明抑制外泌体ITGB2或恢复DC功能可能改善TNBC的治疗结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Iranian Journal of Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH-

CiteScore

2.20

自引率

7.10%

发文量

300

审稿时长

3-8 weeks

期刊介绍： Iranian Journal of Public Health has been continuously published since 1971, as the only Journal in all health domains, with wide distribution (including WHO in Geneva and Cairo) in two languages (English and Persian). From 2001 issue, the Journal is published only in English language. During the last 41 years more than 2000 scientific research papers, results of health activities, surveys and services, have been published in this Journal. To meet the increasing demand of respected researchers, as of January 2012, the Journal is published monthly. I wish this will assist to promote the level of global knowledge. The main topics that the Journal would welcome are: Bioethics, Disaster and Health, Entomology, Epidemiology, Health and Environment, Health Economics, Health Services, Immunology, Medical Genetics, Mental Health, Microbiology, Nutrition and Food Safety, Occupational Health, Oral Health. We would be very delighted to receive your Original papers, Review Articles, Short communications, Case reports and Scientific Letters to the Editor on the above mentioned research areas.