微环境下肿瘤相关巨噬细胞极化对乳腺癌进展作用*

乳腺癌是女性最为常见、死亡率最高的恶性肿瘤之一。医学技术的进步一定程度上提高了乳腺癌患者的存活率，但后期化疗产生的耐药导致很多患者在短期内复发或转移。肿瘤微环境（tumor microenvironment，TME ）中肿瘤相关巨噬细胞（tumor associated macrophages，TAMs）对癌细胞的多重影响作用是当前研究的热点。TAMs具有高度可塑性，不同刺激后可极化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），M1和M2型巨噬细胞是TAMs功能表现的两个极端。M2型TAMs和乳腺癌的生长、耐药及预后密切相关，探索促进巨噬细胞向M2方向极化的机制有助于发现乳腺癌新的免疫治疗靶点，选择性控制TAMs亚型转换可能有助于加强化疗效果。本文对极化巨噬细胞的主要功能及其作用机制进行阐述，旨在为乳腺癌的免疫治疗提供新的策略。

Effect of macrophage polarization on breast cancer progression under tumor associated microenvironment

Breast carcinoma is one of the most common and deadly malignant tumors in women. Although surgical resection improves the survival, chemotherapy resistance of breast cancer cells leads to frequent causes of intrahepatic spread and extrahepatic metastasis. Tumor-associated macrophages (TAM) have been studied extensively for their relationship with tumor cells and their multi-facet 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. The intent of this review is to describe the main function of the two types of polarization states in TAM, and to gain understanding of the mechanisms involved in the immunotherapy of breast cancer.