肿瘤相关巨噬细胞肝X受体的激活对抗瘤应答的影响

［摘要］目的： 研究肿瘤微环境、肝X受体（ liver X receptors,LXRs）与肿瘤相关巨噬细胞（tumor associated macrophage， TAM）的形成及其功能之间的关系。方法： 提取肿瘤组织中的肿瘤相关巨噬细胞，同时提取腹腔巨噬细胞作为对照。在体外实验中巨噬细胞与肿瘤细胞共培养或者使用肿瘤上清处理巨噬细胞， 实时PCR检测巨噬细胞LXRs、IL 10、IL 12的mRNA水平；分别激活LXR和阻断LXR信号通路，观察其对TAM形成的影响。结果： 肿瘤微环境可诱导巨噬细胞LXRs受体高表达，并表现为M2型巨噬细胞的表型，激活LXRs可以促进巨噬细胞向TAM转变，而阻断LXR信号通路则抑制TAM的形成。 结论： 肿瘤微环境能激活LXRs，从而诱导TAM的形成，并促进肿瘤生长、转移和免疫逃逸。

Tumor-associated macrophage impacts anti-tumor responses through activation of liver X receptors

Objective: To investigate the connection between tumor microenvironment and liver X receptors(LXRs),and their function on the development of tumor-associated macrophage.Methods: Macrophages were sorted from tumor tissue and peritoneal lavage fluid,the expression level of LXRs,IL10 and IL12 were determined by real-time PCR.The internal relations among microenvironment,LXR receptors and TAM were explored in seperated experiments as follows: Macrophages cell line RAW264.7 were co-cultured with tumor cell line TC-1,or treated with tumor supernatant or LXR agonists,or the LXR signaling pathway in macrophages were blocked,then the phenotypes and functions of macrophages were determined.Results: Tumor microenvironment could promote the expression of LXR receptors,and induce the M2 subset phenotype of macrophages.The activation of LXR receptors could also induce the M2 phenotype,and the effect could be reversed when the LXR signaling pathway in macrophages were blocked.Conclusion: LXR could be activated by tumor microenvironment,then induce the accumulation of TAM,and activate their function on promote the growth,metastasis,and immune evasion of tumor.