From blood draw to tumor infiltration: therapeutic variations in CAR-macrophage therapy for solid tumors

INTRODUCTION: Engineering CAR-macrophages (CAR-Ms) has revolutionized the solid tumors immunotherapy, due to intrinsic anti-tumor capacity, phagocytosis ability, and immunomodulatory effects of macrophages in tumor microenvironment (TME) remodeling. METHODOLOGY: A literature review was conducted using databases including PubMed, Google Scholar, and Scopus. The data was extracted using relevant articles published from 1991 to 2026 based on key words such as Chimeric Antigen Receptor Macrophages, CAR-M, Immunotherapy Resistance, Solid Tumors, and Tumor Microenvironment. AREAS COVERED: CAR-Ms originate from different sources, but in turn come with distinct advantages and challenges regarding scalability, polarization capacity, phenotype shift, antigen escape, and functional stability. Genetic engineering techniques are essential to increase CAR-M efficacy. Along with intrinsic engineering, the integration of CAR-Ms with chemotherapy, radiotherapy, immune checkpoint inhibitors, and new methods, such as nanomedicine, enhances antitumor effects by modulating TME barriers and abrogation of immune evasion mechanisms. EXPERT OPINION/COMMENTARY: CAR-m therapy is represented as a promising next-generation treatment for solid tumors, due to its strength to overcome the challenges of lymphocyte approaches. However, TME polarization and variability in patient response should be considered to achieve optimal efficacy. Future advancements should improve signaling design, integration of novel immunologic methods, TME modulation, and biomarker-guided patient stratification.