Ge Wenke, Wu Weibing
Department of Thoracic Surgery, The First Clinical Medical College of Nanjing Medical University, Nanjing 210000, China.
Zhongguo Fei Ai Za Zhi. 2023 Mar 20;26(3):228-237. doi: 10.3779/j.issn.1009-3419.2023.106.07.
Tumor-associated macrophages (TAMs), characterized by high plasticity, are the most abundant immune cells in the tumor microenvironment (TME). TAMs are recruited to tumor region in response to various TME components such as cytokines, chemokines as well as exosomes. Subsequently, these environmental cues induce a certain polarization state of TAMs, ranging from anti-tumor states (M1-like) to pro-tumor states (M2-like). Furthermore, the polarization process of TAMs is continuous and gradually inclines toward the M2-like state with malignant progression, forming a positive feedback loop that facilitates tumor growth and metastasis. Consequently, figuring out the factors and mechanisms affecting TAMs polarization is beneficial for developing novel therapeutic strategies that can be combined with other immunotherapies for lung cancer. In previous studies, many significant molecules and pathways which could promote the M2 polarization of TAMs were identified. However, the underlying mechanisms of this sophisticated cross-talk between tumor cells, stroma cells and TAMs remain still difficult to by fully understand. In this review, we summarize the comprehensive factors involved in triggering TAMs polarization towards the M2 phenotype and further explore the relevant molecular mechanisms. .
肿瘤相关巨噬细胞(TAM)具有高度可塑性,是肿瘤微环境(TME)中最丰富的免疫细胞。TAM会响应各种TME成分(如细胞因子、趋化因子以及外泌体)而被招募至肿瘤区域。随后,这些环境信号会诱导TAM进入特定的极化状态,范围从抗肿瘤状态(M1样)到促肿瘤状态(M2样)。此外,TAM的极化过程是持续的,并且随着恶性进展逐渐倾向于M2样状态,形成促进肿瘤生长和转移的正反馈回路。因此,弄清楚影响TAM极化的因素和机制,有助于开发可与其他肺癌免疫疗法联合使用的新型治疗策略。在先前的研究中,已鉴定出许多可促进TAM向M2极化的重要分子和信号通路。然而,肿瘤细胞、基质细胞和TAM之间这种复杂相互作用的潜在机制仍难以完全理解。在本综述中,我们总结了引发TAM向M2表型极化的综合因素,并进一步探讨了相关分子机制。