Li Qian, Xu Jingwei, Hua Runjia, Xu Hanye, Wu Yongyou, Cheng Xiaju
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, P. R. China.
Department of Thoralic Surgery, Suzhou Municipal Hospital Institution, Suzhou 215000, P. R. China.
J Cancer. 2025 Mar 31;16(7):2261-2274. doi: 10.7150/jca.108194. eCollection 2025.
Tumor-associated macrophages (TAMs) are one type of the most abundant immune cells within tumor, resulting in immunosuppresive tumor microenvironment and tumor resistance to immunotherapy. Thus, targeting TAMs is a promising therapeutic strategy for boosting cancer immunotherapy. This study provides an overview of current therapeutic strategies targeting TAMs, which focus on blocking the recruitment of TAMs by tumors, regulating the polarization of TAMs, and directly eliminating TAMs using various nanodrugs, especially with a new categorization based on the specific signaling pathways, such as NF-κB, HIF-1α, ROS, STAT, JNK, PI3K, and Notch involved in their regulatory mechanism. The latest developments of nanodrugs modulating these pathways are discussed in determining the polarization of TAMs and their role in the tumor microenvironment. Despite the challenges in clinical translation and the complexity of nanodrug synthesis, the potential of nanodrugs in enhancing the effectiveness of cancer immunotherapy is worthy of expecting.
肿瘤相关巨噬细胞（TAM）是肿瘤内最丰富的免疫细胞类型之一，会导致免疫抑制性肿瘤微环境以及肿瘤对免疫疗法产生抗性。因此，靶向TAM是增强癌症免疫疗法的一种有前景的治疗策略。本研究概述了当前靶向TAM的治疗策略，这些策略侧重于通过肿瘤阻断TAM的募集、调节TAM的极化，以及使用各种纳米药物直接消除TAM，特别是基于参与其调节机制的特定信号通路（如NF-κB、HIF-1α、ROS、STAT、JNK、PI3K和Notch）进行新的分类。在确定TAM的极化及其在肿瘤微环境中的作用时，讨论了调节这些通路的纳米药物的最新进展。尽管在临床转化方面存在挑战且纳米药物合成复杂，但纳米药物在增强癌症免疫疗法有效性方面的潜力值得期待。
