ABSTRACT

Triple-Negative Breast Cancer (TNBC) is a more aggressive and heterogeneous form of breast cancer that lacks the expression of estrogen receptor, progesterone receptor and HER2, leaving few therapeutic options and an unfavorable prognosis. The ability of tumor cells to escape from the immune system of the host is emerging as an essential mechanism for the progression, metastasis and resistance to treatment of TNBC. Immune checkpoint pathways and HLA-G, a non-classical major histocompatibility complex molecule with strong immunosuppressive effects, are among the most crucial immunoregulatory mechanisms that play part in this process. Aberrant HLA-G expression reduces the ability of natural killer cells, CTLs and APCs to attack and destroy tumors, and allows them to survive and escape the immune system.
The recent development of novel CRISPR-Cas9 applications for the specific immunogenetic modulation of cancer therapy. Gene editing using a CRISPR strategy is a promising method to restore antitumor immunity in TNBC by precisely editing genes linked to immune checkpoint signaling and tumor associated immunosuppressive pathways. Furthermore, combination treatments with a combination of HLA-G and checkpoint inhibitors like PD-1/PD-L1 and CTLA-4 might be more effective for immune-mediated tumor clearance and less prone to resistance.
The immunobiological functions of HLA-G and immune checkpoints in TNBC are reviewed and recent advances in therapeutic approaches with CRISPR technology against these pathways are summarized. In addition, the review reviews the challenges encountered in the delivery, off-target effects, tumour heterogeneity, and clinical safety of these treatments. In summary, immune escape modulation with CRISPR is a swiftly developing approach that may have great promise in precision immunotherapy and ultimately clinical outcomes for TNBC patients.

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Cite this article

Dhaidan, N. I. (2026). Crispr-Based Modulation of Hla-G and Immune Checkpoint Networks in Triple-Negative Breast Cancer: Emerging Immunogenetic Approaches for Overcoming Tumor Immune Escape. INTERNATIONAL JOURNAL OF HEALTH & MEDICAL RESEARCH, 5(5), 485-492. https://doi.org/10.58806/ijhmr.2026.v5i5n21