Recent progress in immune evasion mechanisms of triple-negative breast cancer

Significant progress has been made in understanding the complex immune evasion mechanisms of triple-negative breast cancer (TNBC), paving the way for more effective immunotherapies. This review highlights key advances in elucidating the molecular basis of TNBC immune escape, including aberrant immune checkpoint expression, metabolic reprogramming, epigenetic regulation, immune evasion by associated cellular components, and clinical trials of emerging immunotherapies. Specifically, overexpression of immune checkpoint inhibitors such as PD-L1 on TNBC cells and within the tumor microenvironment (TME) plays a critical role in suppressing antitumor immunity. Secondly, TNBC cells evade immune surveillance through metabolic reprogramming. For instance, upregulated glutamine metabolism supports tumor growth and modulates the TME toward immunosuppression by limiting nutrient availability to immune cells. Competitive consumption of amino acids such as tryptophan and arginine further compromises immune cell function, promoting immune escape. Epigenetic modifications, including DNA methylation and histone modifications, are increasingly recognized as key contributors to immune evasion in TNBC. These mechanisms can silence genes involved in antigen presentation and immune activation while promoting the expression of immunosuppressive factors. Long non-coding RNAs (lncRNAs) have been identified as central regulators of immune evasion in TNBC, offering new therapeutic targets for intervention. Moreover, TNBC actively shapes its microenvironment to establish immunosuppression, including recruitment of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2-polarized macrophages, which collectively inhibit effector T cell function. Building on these mechanistic insights, this review also integrates findings from clinical trials evaluating next-generation immunotherapies, including bispecific antibodies targeting PD-1/CTLA-4, LAG-3 inhibitors, and CD47-SIRPα blockers, as well as potential biomarkers. These novel combination strategies aim to overcome resistance to single-agent checkpoint inhibitors, while research explores monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates (ADCs) within biomarker-driven personalized treatment frameworks. The ultimate goal is to improve survival and quality of life for TNBC patients through tailored immunotherapies.