Cao Xinyu, Wan Shen, Wu Bingyu, Liu Zhikuan, Xu Lixing, Ding Yu, Huang Haiqin
Department of Pharmaceutics, School of Pharmacy, Nantong University, Nantong 226001, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
Mol Pharm. 2025 Mar 3;22(3):1174-1197. doi: 10.1021/acs.molpharmaceut.4c01277. Epub 2025 Jan 27.
The development of malignant tumors is a complex process that involves the tumor microenvironment (TME). An immunosuppressive TME presents significant challenges to current cancer therapies, serving as a key mechanism through which tumor cells evade immune detection and play a crucial role in tumor progression and metastasis. This impedes the optimal effectiveness of immunotherapeutic approaches, including cytokines, immune checkpoint inhibitors, and cancer vaccines. Tumor-associated macrophages (TAMs), a major component of tumor-infiltrating immune cells, exhibit dual functionalities: M1-like TAMs suppress tumorigenesis, while M2-like TAMs promote tumor growth and metastasis. Consequently, the development of various nanocarriers aimed at polarizing M2-like TAMs to M1-like phenotypes through distinct mechanisms has emerged as a promising therapeutic strategy to inhibit tumor immune escape and enhance antitumor responses. This Review covers the origin and types of TAMs, common pathways regulating macrophage polarization, the role of TAMs in tumor progression, and therapeutic strategies targeting TAMs, aiming to provide a comprehensive understanding and guidance for future research and clinical applications.
恶性肿瘤的发展是一个涉及肿瘤微环境(TME)的复杂过程。免疫抑制性肿瘤微环境给当前的癌症治疗带来了重大挑战,它是肿瘤细胞逃避免疫检测的关键机制,并在肿瘤进展和转移中起关键作用。这阻碍了免疫治疗方法(包括细胞因子、免疫检查点抑制剂和癌症疫苗)的最佳疗效。肿瘤相关巨噬细胞(TAM)是肿瘤浸润免疫细胞的主要成分,具有双重功能:M1样TAM抑制肿瘤发生,而M2样TAM促进肿瘤生长和转移。因此,通过不同机制将M2样TAM极化为M1样表型的各种纳米载体的开发已成为一种有前景的治疗策略,以抑制肿瘤免疫逃逸并增强抗肿瘤反应。本综述涵盖了TAM的起源和类型、调节巨噬细胞极化的常见途径、TAM在肿瘤进展中的作用以及针对TAM的治疗策略,旨在为未来的研究和临床应用提供全面的理解和指导。