乳腺癌微环境下肿瘤相关巨噬细胞的极化研究进展

Mechanism of macrophage polarization in breast cancer associated microenvironment

乳腺癌是女性死亡率最高的恶性肿瘤之一。尽管外科切除术在一定程度上提高了乳腺癌患者的存活率,但肿瘤细胞在后期化疗过程中产生的耐药导致很多患者在化疗后仍会出现短期内的复发或转移。肿瘤微环境(TME)中肿瘤相关巨噬细胞(TAM)对肿瘤细胞的多重影响作用是当前研究的热点。TAM具有高度可塑性,经不同刺激可极化分型为经典活化的促炎性巨噬细胞(M1型)和替代活化的免疫抑制巨噬细胞(M2型),极化后的M1和M2型巨噬细胞是TAM功能表现的两个极端,其中M2型TAM被认为与乳腺癌的生长、耐药及预后密切相关。探索乳腺癌微环境中巨噬细胞极化的功能机制有助于揭示针对乳腺癌新的免疫治疗靶点,通过选择性控制TAM亚型的转换有利于增强化疗效果。本文对TME中极化巨噬细胞的主要功能及其在药物干预下互相转化中的作用机制进行论述,旨在为乳腺癌的免疫治疗提供新的策略。

Breast cancer is one of the most lethal malignancies in women. Although surgical resection improves survival, chemotherapy resistance of breast cancer cells lead to recurrence and metastasis in a short time. Tumor-associated macrophages (TAM) have been studied extensively for their relationship with tumor cells and their multi-faceted functions in the tumor microenvironment (TME). Recent research provides strong support for dual roles of TAM, highly plastic, both beneficial and destructive, as well as differential activation of these immune cells into one of at least two phenotypes, M1 (classically activated type I) or M2 (alternatively activated). It has been indicated that TAM express several M2-associated pro-tumor functions, including promotion of angiogenesis, suppression of adaptive immunity, resistance and prognosis. Identification of mechanisms promoting functional diversion of macrophages towards an M2 direction may disclose new valuable therapeutic targets against tumors. Anti-tumor agents with selective restoration of an M1 phenotype or switching of infiltrating M2 macrophages towards an M1 phenotype in TAM may promote anti-tumor activities. In this paper, the main function of the two types of polarization states in TAM and the mechanism of their interaction under drug intervention are discussed, in order to provide a new strategy for immunotherapy of breast cancer.