肿瘤微环境中肿瘤相关巨噬细胞极化的影响因素及其意义

Influencing Factors and Significance of Tumor-associated Macrophage Polarization in Tumor Microenvironment

肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)具有极高的可塑性,是肿瘤微环境(tumor microenvironment,TME)中含量最丰富的免疫细胞。各种TME成分(如细胞因子、趋化因子以及外泌体等)将TAMs招募到肿瘤区域内。随后,这些环境因子把TAMs诱导为抗肿瘤状态(M1样)或促肿瘤状态(M2样)之间的某一极化状态。另外,TAMs的极化过程是连续的,并且会随着肿瘤恶性进展而逐渐地朝向M2样状态,构成了一个有利于肿瘤生长和转移的正反馈环。因此,深入研究影响TAMs极化的各种因素和机制,有助于研发一种新的且可以与其他免疫治疗相结合的肺癌治疗策略。在既往的研究中已发现了许多可以促进TAMs的M2极化的分子和通路。然而,肿瘤细胞、间质细胞和TAMs之间这种复杂的串扰的潜在机制仍然难以研究清楚。在这篇综述中我们总结了促进TAMs向M2表型极化的各种因素,并进一步探讨了相关的分子机制。

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.