Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies

Macrophages are increasingly emerging as a powerful platform for next-generation cell therapies. In this open-access review, published in Signal Transduction and Targeted Therapy, the authors provide a comprehensive overview of macrophage biology, signaling pathways, and engineering strategies that are shaping the future of immunotherapy.

The article explores how advances in our understanding of macrophage development, tissue plasticity, metabolism, and immune signaling are enabling the design of more effective therapeutic cells. Particular focus is placed on genetically engineered macrophages, including CAR-macrophages (CAR-Ms), which combine innate immune functions with antigen-specific targeting and show significant promise for the treatment of solid tumors and other diseases.

Beyond therapeutic concepts, the review discusses key translational challenges such as scalable manufacturing, standardization, and regulatory considerations that must be addressed to bring macrophage-based therapies into clinical practice. Bringing together fundamental immunology and emerging cell engineering technologies, this review highlights the growing potential of macrophages as versatile therapeutic agents across oncology, inflammatory, infectious, fibrotic, and neurodegenerative diseases.