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

Puerkaiti  Paierhati; Binlin  Ma; Muzhapaer  Abudukeremu

doi:10.18502/ijph.v54i6.18903

Puerkaiti Paierhati Department of Breast and Thyroid Surgery, the Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Oncology, Urumqi, 830011, China
Binlin Ma Department of Breast and Thyroid Surgery, the Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Oncology, Urumqi, 830011, China
Muzhapaer Abudukeremu Department of Breast and Thyroid Surgery, the Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Oncology, Urumqi, 830011, China

DOI: https://doi.org/10.18502/ijph.v54i6.18903

Keywords: Triple-negative breast cancer; Dendritic cell; Exosome

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.