Wang Lei, Hu Ziyi, Zhang Wencan, Wang Zhixin, Cao Ming, Cao Xu
Shanghai Frontiers Science Center for Drug Target Identification and Delivery, and the Engineering Research Center of Cell and Therapeutic Antibody of the Ministry of Education, School of Pharmaceutical Sciences, National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
Biochem Pharmacol. 2025 Feb;232:116712. doi: 10.1016/j.bcp.2024.116712. Epub 2024 Dec 13.
Cancer therapy has been revolutionized by immunotherapeutic agents exploiting adaptive antitumor immunity in the past two decades. However, the overall response rate of these immunotherapies is limited, and patients also develop resistance upon treatment, promoting a rapidly growing exploration of anti-tumor innate immunity for effective cancer therapy. Among these, macrophage immunotherapy through harnessing macrophage phagocytosis has been thrust into the spotlight due to its potential for simultaneously inducing cancer cell killing effect and mobilizing adaptive antitumor responses. Here in this review, we summarize the current macrophage immunotherapy such as therapeutic antibodies, phagocytosis checkpoint blockades, and CAR-macrophages with a particular emphasis on the resistant mechanisms limiting their therapeutic effects. Moreover, we further survey the efforts being placed to seek synergistic mechanisms and combination strategies for promoting macrophage phagocytosis which might stand as next-generation cancer immunotherapy.
在过去二十年中，利用适应性抗肿瘤免疫的免疫治疗药物彻底改变了癌症治疗方式。然而，这些免疫疗法的总体缓解率有限，并且患者在治疗后也会产生耐药性，这促使人们对有效的癌症治疗中抗肿瘤固有免疫进行快速发展的探索。其中，通过利用巨噬细胞吞噬作用的巨噬细胞免疫疗法因其具有同时诱导癌细胞杀伤作用和调动适应性抗肿瘤反应的潜力而备受关注。在本综述中，我们总结了当前的巨噬细胞免疫疗法，如治疗性抗体、吞噬检查点阻断和嵌合抗原受体巨噬细胞，特别强调了限制其治疗效果的耐药机制。此外，我们进一步探讨了为促进巨噬细胞吞噬作用而寻求协同机制和联合策略的努力，这可能成为下一代癌症免疫疗法。
