The article "Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy" by Shuaixi Yang et al. highlights the significant role of macrophages in the tumor microenvironment (TME) and their potential in cancer immunotherapy. The authors discuss the rapid evolution of bioengineering technology and its application in creating engineered macrophages for various therapeutic purposes, including drug delivery, chimeric antigen receptor (CAR) macrophage therapy, and synergistic treatments involving bacterial outer membrane vesicles (OMVs) and macrophages. Key points include: 1. **Macrophages in the TME**: Macrophages play crucial roles in maintaining tissue homeostasis, regulating cancer progression, and defending against pathogens. They can exhibit both pro- and anti-tumor effects, depending on their polarization state (M1 or M2). 2. **Engineered Macrophages for Drug Delivery**: Engineered macrophages can act as direct or indirect drug carriers, enhancing the efficacy of anticancer drugs by overcoming immune barriers and improving drug targeting. 3. **CAR-M Cell Therapy**: Chimeric antigen receptor-modified macrophages (CAR-Ms) have shown promise in targeted therapy against specific tumor antigens, offering a more precise and efficient treatment option compared to CAR-T-cell therapy. 4. **OMVs and Macrophages**: OMVs, naturally occurring nanoparticles secreted by gram-negative bacteria, can be modified to target the TME and enhance the therapeutic efficacy of macrophages. They can be used to deliver therapeutic agents, block immunosuppressive pathways, and improve the targeting of macrophages to tumor sites. 5. **Clinical Trials and Future Outlook**: While significant progress has been made, challenges remain, including the need to understand the mechanisms governing macrophage recruitment and polarization in the TME, the safety and efficacy of engineered macrophages, and the cost and patient requirements for clinical translation. The article concludes that engineered macrophages represent a promising new frontier in cancer immunotherapy, with the potential to revolutionize the treatment of solid tumors by harnessing the power of the immune system. However, further research is needed to address the remaining challenges and optimize these therapies for clinical application.The article "Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy" by Shuaixi Yang et al. highlights the significant role of macrophages in the tumor microenvironment (TME) and their potential in cancer immunotherapy. The authors discuss the rapid evolution of bioengineering technology and its application in creating engineered macrophages for various therapeutic purposes, including drug delivery, chimeric antigen receptor (CAR) macrophage therapy, and synergistic treatments involving bacterial outer membrane vesicles (OMVs) and macrophages. Key points include: 1. **Macrophages in the TME**: Macrophages play crucial roles in maintaining tissue homeostasis, regulating cancer progression, and defending against pathogens. They can exhibit both pro- and anti-tumor effects, depending on their polarization state (M1 or M2). 2. **Engineered Macrophages for Drug Delivery**: Engineered macrophages can act as direct or indirect drug carriers, enhancing the efficacy of anticancer drugs by overcoming immune barriers and improving drug targeting. 3. **CAR-M Cell Therapy**: Chimeric antigen receptor-modified macrophages (CAR-Ms) have shown promise in targeted therapy against specific tumor antigens, offering a more precise and efficient treatment option compared to CAR-T-cell therapy. 4. **OMVs and Macrophages**: OMVs, naturally occurring nanoparticles secreted by gram-negative bacteria, can be modified to target the TME and enhance the therapeutic efficacy of macrophages. They can be used to deliver therapeutic agents, block immunosuppressive pathways, and improve the targeting of macrophages to tumor sites. 5. **Clinical Trials and Future Outlook**: While significant progress has been made, challenges remain, including the need to understand the mechanisms governing macrophage recruitment and polarization in the TME, the safety and efficacy of engineered macrophages, and the cost and patient requirements for clinical translation. The article concludes that engineered macrophages represent a promising new frontier in cancer immunotherapy, with the potential to revolutionize the treatment of solid tumors by harnessing the power of the immune system. However, further research is needed to address the remaining challenges and optimize these therapies for clinical application.