Immunoglobulin-binding protein and Toll-like receptors in immune landscape of breast cancer

• Published in: Life sciences (1973) 2024-12, Vol.358, p.123196, Article 123196
• Main Authors: Bhamidipati, Priyamvada, Nagaraju, Ganji Purnachandra, Malla, RamaRao
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Drug Resistance, Neoplasm - immunology; Endoplasmic Reticulum Chaperone BiP; Female; Humans; Immune landscape; Immunoglobulin-binding protein; Signal Transduction; TME; Toll-like receptor; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; Triple Negative Breast Neoplasms - immunology; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumor Microenvironment - immunology; Unfolded Protein Response - immunology
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2024.123196

Breast cancer (BC) is a complex disease exhibiting significant heterogeneity and encompassing various molecular subtypes. Among these, triple-negative breast cancer (TNBC) stands out as one of the most challenging types, characterized by its aggressive nature and poor prognosis. This review embarks on a comprehensive exploration of the immune landscape of BC, with a primary focus on the functional and structural characterization of immunoglobulin-binding protein (BiP) and its pivotal role in regulating the unfolded response (UPR) pathway of proteins. Moreover, we unravel the multifaceted functions of BiP in BC, with a special emphasis on the involvement of cell surface BiP in TNBC metastasis, drug resistance, and its contribution to the formation of the tumor microenvironment (TME). We also provide mechanistic insights into how ER-resident BiP mediates the sensitization of drug-resistant BC to different treatment strategies, thereby offering promising avenues for therapeutic intervention. We also delve into the role of Toll-like receptors (TLRs), shedding light on their diverse expression patterns across BC and their influence on modulating the tumor immune response. Understanding the interplay between BiP, TLRs, and the immune response, especially in TNBC, opens avenues for novel immunotherapies. Future research should focus on developing targeted therapies that activate ER-resident BiP or inhibit cell surface BiP, and modulate TLR signaling. Moreover, exploring BiP as a biomarker for TNBC diagnosis, prognosis, and treatment response will be crucial for personalized medicine. Represents BiP mediated drug induced chemoresistance and drug sensitization. Binding of chemotherapeutic drug at N-terminal NBD domain of BiP leads to drug resistance while binding at C-terminal SBD domain leads to sensitization of TNBC cells to chemotherapeutic drugs. [Display omitted] •BiP and TLRs contribute to ICD by recognizing DAMPs from dying cancer cells.•ER-resident BiP contributes to the immune response against BC.•Membrane bound BiP mediates metastasis and drug resistance in BC.•Natural compounds sensitize BC cells by targeting ER-resident BiP.•Toll-like receptors mediate immune response against BC.