肿瘤相关巨噬细胞（TAM）被认为与多个肿瘤的疾病进展相关，但巨噬细胞极化在前列腺癌中的作用机制却不清楚。在前期工作中，我们诱导了M1、M2、TAM，发现TAM中let-7b、let-7c表达显著增高；同时M1中IL-6、IL-12、IL-1b表达增高，而IL-10只在TAM中高表达。由于SOCS1涉及广泛的细胞因子分泌，为let-7的潜在靶标，因此我们推测巨噬细胞可能受到let-7和SOCS1调控，其表型转变可能涉及JAK2/STAT3并影响前列腺癌疾病进展。本研究拟通过前列腺癌细胞与原代巨噬细胞的共培养来研究let-7与SOCS1、JAK2/STAT3通路的联系，分析它们调控的巨噬细胞极化对前列腺癌进展的影响，并通过裸鼠实验和病例-对照进行验证。探明let-7-SOCS1在巨噬细胞转变中的作用，探讨巨噬细胞极化对前列腺癌进程的影响，寻找前列腺癌免疫调控网络的关键节点和治疗靶点。

Tumor-associated macrophages (TAMs) are related to the development of several kinds of tumors，but how the macrophage polarization works in prostate cancer is still unknown. In previous work, we have already induced macrophages of different phenotypes including M1,M2 and TAM and found that consistent upregulation of expression of microRNA let-7b and let-7c are characteristics of prostatic TAM. We have also observed that the expression of IL-6,IL-12,IL-1β mRNA increased significantly in M1,while the expression of IL-10 was up-regulated only in TAM. Suppressor of cytokine signaling 1(SOCS1) involves in a huge number of cytokines and is regarded as a potential target of let-7, therefore, we hypothesize that macrophage M1/M2 polarization may be under the regulation of miRNAlet-7 and SOCS1, which may regulate JAK2/ STAT3 signaling, and then the changed macrophage may affect the progression of prostate cancer. In this project, the co-culturing model of primary macrophages and prostate cancer cell lines is used to study the association among let-7, SOCS1 and JAK2/ STAT3 signaling, and analyze the influence of macrophage polarization mediated by these molecules on prostate cancer cells. The results will be tested through nude mice experiments and case - control study. The project aims to investigate the mechanism of macrophage polarization mediated by let-7-SOCS1-JAK2/STAT3 pathway and how the changed macrophage affects prostate cancer progression, and find the key node of immune regulatory network and the therapeutic targets in prostate cancer.