Mast cells in tumors: dual roles and therapeutic potential

Mast cells (MCs) are tissue-resident immune cells that accumulate in the tumor microenvironment (TME) and display marked functional plasticity. Rather than acting through fixed pro-tumor or anti-tumor phenotypes, tumor-associated MCs acquire functional programs shaped by tumor type, spatial localization, disease stage, and local microenvironmental cues. In this review, we organize these dual roles around cellular crosstalk, mediator release, angiogenic and lymphangiogenic regulation, and extracellular matrix remodeling. Through these interconnected mechanisms, MCs may either promote tumor progression by reinforcing immunosuppression, limiting effector T cell activity, and supporting vascular, lymphatic, and stromal remodeling, or contribute to tumor suppression by promoting tumor cell apoptosis, antigen presentation, cytotoxic immune-cell recruitment, and anti-tumor mediator release. We also examine MC responses to various cancer treatments, including physical treatment modalities, chemotherapy, immunotherapy, targeted therapy, and CAR-based cell therapies, and discuss how these responses may influence therapeutic efficacy and treatment-related toxicity. Furthermore, we highlight emerging MC-targeted strategies that either suppress their chronic pro-tumor secretion or intentionally induce acute anti-tumor degranulation. By deciphering the dual nature of MCs in cancer, this review underscores the potential for reprogramming MCs to improve tumor treatment outcomes.