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

Sep 23, 2026

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Study evaluates exosomal integrin beta-2 (ITGB2) released by triple-negative breast cancer (TNBC) cells and its ability to reshape immune responses through interaction with Toll-like receptor 4 (TLR4) in dendritic cells (DCs). The work tests how ITGB2 supports an immunosuppressive tumor microenvironment by reducing DC activation, maturation, and cytokine output. Methods quantify ITGB2 in TNBC tissues and cell lines and use ITGB2 knockdown or overexpression, followed by DC co-culture with exosomes.

LanguageEnglish

CategoryHealthcare

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Pages11

Reading Time28 min

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Abstract

Background

Methods

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Introduction

Materials and Methods

Iran J Public Health, Vol. 54, No.6, Jun 2025, pp.1252-1262 Original Article Exosomal ITGB2 Mediates Immune Evasion in Triple-Negative Breast Cancer by Suppressing Dendritic Cell Activation via TLR4 PuerkaitiPaierhati 1,2, *Binlin Ma 1,2, *MuzhapaerAbudukeremu 1,2 1. Department of Breast and Thyroid Surgery, the Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Oncology, Urumqi, 830011, China 2. The Clinical Medical Research Center ofBreast and Thyroid Tumor in Xinjiang, Urumqi, 830011, China *[Corresponding Authors:](Corresponding Authors: Emails: doctormmxy@aliyun.com)[ Emails: doctormmxy@aliyun.com](Corresponding Authors: Emails: doctormmxy@aliyun.com), [hbyxzzs@sina.cn](hbyxzzs@sina.cn)[ ](hbyxzzs@sina.cn)(Received 12 Feb 2025; accepted 18 Apr 2025) 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. Keywords: Triple-negative breast cancer; Dendritic cell; Exosome Introduction Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, comprising 10% -20% of all cases. It is characterized by the absence of estrogen receptors, progesterone receptors, and HER2 amplification. TNBC is associated with a poor prognosis due to its high recurrence and metastatic potential, and it lacks targeted therapies, leaving chemotherapy as the primary treatment, which often yields suboptimal results (1,2) . One of the key challenges in TNBC is its immunosuppressive tumor microenvironment, which promotes tumor progression and resistance to therapy. Exosomes, small extracellular vesicles secreted by cells, play a crucial role in modulating the tumor microenvironment. They carry bioactive molecules such as proteins, lipids, Copyright © 2025 Paierhati et al. Published by Tehran University of Medical Sciences. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International license. ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)). Non-commercial uses of the work are permitted, provided the original work is properly cited DOI: [https://doi.org/10.18502/ijph.v54i6.18903](https://doi.org/10.18502/ijph.v54i6.18903) 1252 Available at: [http://ijph.tums.ac.ir](http://ijph.tums.ac.ir) Paierhati et al.: ExosomalITGB2 Mediates Immune Evasion in Triple-Negative… and nucleic acids, which influence recipient cells. In TNBC, exosomes contribute to immune evasion and metastasis (3) . Integrin beta-2 (ITGB2), also known as CD18, is a key leukocyte integrin involved in cell adhesion and signaling (4) . ITGB2 forms heterodimers with alpha subunits, creating integrins like LFA-1

FAQs

What is the main focus of the study?

The study examines how exosomal ITGB2 from TNBC cells affects immune responses by interacting with TLR4 signaling in dendritic cells.

How were ITGB2 effects tested experimentally?

ITGB2 expression in TNBC tissues and cell lines was measured by qPCR and Western blot, and ITGB2 knockdown/overexpression was created in MDA-MB-231 cells to assess effects on TLR4 in DCs.

What immune outcome did exosomal ITGB2 produce?

Exosomal ITGB2 suppressed TLR4 expression in DCs, impairing DC maturation and decreasing cytokine secretion, thereby promoting an immunosuppressive microenvironment.

Sep 23, 2026

Uploaded by Aditya