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<p>Breast cancer remains the most frequently diagnosed malignancy among women worldwide and continues to pose significant challenges due to its heterogeneity and complex interactions with the immune system. Recent advances in tumor immunology have revealed that progression is not solely driven by malignant epithelial cells but is profoundly influenced by immune regulation within the tumor microenvironment. This review synthesizes current knowledge on classical immune players while emphasizing novel insights into emerging immune cell populations including regulatory B cells, tumor-associated neutrophils, and innate lymphoid cells that contribute to immunosuppression, angiogenesis, and metastatic dissemination. In parallel, attention is directed toward non-classical immune checkpoints such as IDO1, IL4I1, VISTA, and TIGIT, which mediate immune escape through metabolic and signaling pathways distinct from the PD-1/PD-L1 axis. The review further explores the clinical implications of these discoveries, highlighting the potential of combination therapies that integrate immune checkpoint inhibitors with metabolic modulators, the development of immune-based biomarkers for predicting progression, and the promise of personalized immunotherapy in aggressive breast cancer subtypes. Future directions emphasize the importance of multi-omics approaches, regional immune profiling, and translational strategies to bridge laboratory findings with clinical application. By consolidating these emerging perspectives, this work provides a comprehensive framework for understanding the evolving role of immune regulation in breast cancer progression and outlines pathways for advancing therapeutic innovation.</p>

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Metabolic enzymes and immune receptors as emerging checkpoints in breast cancer: mechanisms, clinical trials, and therapeutic implications

  • 期刊论文

  • 发表日期：

    2026年4月30日

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  • Abbas S. Neamah

摘要

Breast cancer remains the most frequently diagnosed malignancy among women worldwide and continues to pose significant challenges due to its heterogeneity and complex interactions with the immune system. Recent advances in tumor immunology have revealed that progression is not solely driven by malignant epithelial cells but is profoundly influenced by immune regulation within the tumor microenvironment. This review synthesizes current knowledge on classical immune players while emphasizing novel insights into emerging immune cell populations including regulatory B cells, tumor-associated neutrophils, and innate lymphoid cells that contribute to immunosuppression, angiogenesis, and metastatic dissemination. In parallel, attention is directed toward non-classical immune checkpoints such as IDO1, IL4I1, VISTA, and TIGIT, which mediate immune escape through metabolic and signaling pathways distinct from the PD-1/PD-L1 axis. The review further explores the clinical implications of these discoveries, highlighting the potential of combination therapies that integrate immune checkpoint inhibitors with metabolic modulators, the development of immune-based biomarkers for predicting progression, and the promise of personalized immunotherapy in aggressive breast cancer subtypes. Future directions emphasize the importance of multi-omics approaches, regional immune profiling, and translational strategies to bridge laboratory findings with clinical application. By consolidating these emerging perspectives, this work provides a comprehensive framework for understanding the evolving role of immune regulation in breast cancer progression and outlines pathways for advancing therapeutic innovation.