Shi Binrui, Du Meng, Chen Zhiyi
Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China.
Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Expert Rev Clin Immunol. 2025 Mar;21(3):259-276. doi: 10.1080/1744666X.2024.2438721. Epub 2024 Dec 11.
In recent years, immunotherapy has shown significant therapeutic potential in patients with advanced tumors. However, only a small number of individuals benefit, mainly due to the tumor microenvironment (TME), which provides conditions for the development of tumors. Macrophages in TME, known as tumor-associated macrophages (TAM), are mainly divided into M1 anti-tumor and M2 pro-tumor phenotypes, which play a regulatory role in various stages of tumorigenesis, promote tumorigenesis and metastasis, and cause immunotherapy resistance.
This review focuses on research strategies and preclinical/clinical research progress in translating TAM into antitumor phenotype by referring to the PubMed database for five years. These include small molecule chemotherapy drug development, metabolic regulation, gene editing, physical stimulation, nanotechnology-mediated combination therapy strategies, and chimeric antigen receptor-based immunotherapy.
It is necessary to explore the surface-specific receptors and cell signaling pathways of TAM further to improve the specificity and targeting of drugs and to strengthen research in the field of probes that can monitor changes in TAM in real time. In addition, the physical stimulation polarization strategy has the advantages of being noninvasive, economical, and stable and will have excellent clinical transformation value in the future.
近年来,免疫疗法在晚期肿瘤患者中显示出显著的治疗潜力。然而,只有少数个体受益,主要是由于肿瘤微环境(TME)为肿瘤的发展提供了条件。TME中的巨噬细胞,即肿瘤相关巨噬细胞(TAM),主要分为M1抗肿瘤和M2促肿瘤表型,它们在肿瘤发生的各个阶段发挥调节作用,促进肿瘤发生和转移,并导致免疫治疗耐药。
本综述通过查阅五年的PubMed数据库,重点关注将TAM转化为抗肿瘤表型的研究策略以及临床前/临床研究进展。这些策略包括小分子化疗药物开发、代谢调节、基因编辑、物理刺激、纳米技术介导的联合治疗策略以及基于嵌合抗原受体的免疫疗法。
有必要进一步探索TAM的表面特异性受体和细胞信号通路,以提高药物的特异性和靶向性,并加强对能够实时监测TAM变化的探针领域的研究。此外,物理刺激极化策略具有无创、经济和稳定的优点,未来将具有出色的临床转化价值。