Breast cancer immunotherapy: mechanisms of immune evasion, biomarkers, and emerging therapeutic strategies

Abstract

Breast cancer remains the most prevalent malignancy worldwide and a major cause of cancer-related mortality, representing a heterogeneous and therapeutically challenging disease. Although immunotherapy has revolutionized the treatment of several malignancies, its efficacy in breast cancer is constrained by tumor heterogeneity, low immunogenicity, particularly in hormone receptor (HR)-positive subtypes, and diverse immune evasion mechanisms. This review provides a comprehensive overview of current advances in understanding key mechanisms of breast tumor immune evasion and their overcoming by modern immunotherapy approaches, including immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell therapies, emphasizing biomarker-guided patient selection. We examine the roles of tumor-infiltrating lymphocytes (TILs), tumor mutational burden (TMB), antigen presentation, and programmed death-ligand 1 (PD-L1) expression in the tumor immune evasion and predicting response to immunotherapy. Our main focus is also on emerging strategies, including neoantigen- and DNA/RNA-based vaccines, chimeric and engineered antigen receptors, bispecific T-cell engagers, oncolytic viruses, and targeted immunotherapeutic approaches, which are promising tools for overcoming immune resistance. Furthermore, we evaluate rational combinations of immunotherapy with chemotherapy, radiotherapy, and targeted agents, added by immunosorption as an essential detoxification approach. Finally, we explore future directions emphasizing personalized, multimodal immunotherapy guided by multiomics and spatial profiling, integrated with artificial intelligence. Finally, we synthesize a framework for advancing immunotherapy in breast cancer and identify key areas requiring further translational and clinical investigation.