肿瘤相关巨噬细胞已被证实已被证实能调控微环境中各种免疫细胞的代谢机能，并加速肿瘤生长与转移发挥关键的作用。其确切机制尚未阐明。研究发现,巨噬细胞在肿瘤微环境作用下获得特殊的表型并促进肿瘤发展，其TLR活化诱导免疫耐受。姬松茸是一种珍贵的真菌，初步证实姬松茸多糖显著提高肿瘤免疫应答；检测微环境中巨噬细胞的TLRs受体表达情况结果显示TLR2/4表达明显下调；并抑制TLR2/4下游的IRF-3及NF-κB信号活化，它们的活化与TLR2/4信号活化呈现明显的相关性。另外本课题组分析肿瘤相关巨噬细胞和荷瘤小鼠巨噬细胞的表型，发现其均表达Gr-1+、TLR2和TLR4。据此推测“阻断TLR2/4活化是抑制巨噬细胞向TAM分化的关键因素，也是肿瘤免疫治疗一个新靶点”。本课题拟阐明TLRs与TAM细胞分化内在联系及姬松茸多糖抑制巨噬细胞分化的促免疫应答机制。并进一步细胞、亚细胞水平上探讨姬松茸多糖发挥作用的准确效应靶点。本课题首次在器官、细胞及分子水平上探讨TLRs与M2表型TAM细胞分化内在联系及姬松茸多糖阻断TLR2/4抑制巨噬细胞向TAM分化机制，为肿瘤的免疫治疗提供一种新思路。

Tumor-associated macrophages has been shown to play a key role in promoting tumor progression. The exact mechanism has not been elucidated. The study found, in tumor microenvironment macrophages obtain to specific phenotype and promote tumor development, the activation of TLR induced immune tolerance. Agaricus blazei is a precious fungi,our data showed that by using Agaricus blazei Murill polysaccharides (a TLR2/4 agonist) to treat bone marrow precursors together with NTC-Ms in vivo, the up-regulation of IL-2, IL-12 and IFN-γ; induced by NF-κB and TLR2/4 and IRF-3 were largely inhibited. The treatment by Agaricus blazei Murill polysaccharides retards tumor growth and prolongs the survival of tumor-bearing mice. We have found that monocytes expressing F4/80+CD11b+ from tumor tissue, bone marrow and peripheral blood also express Gr-1 and TLR2 and TLR4. The TLRs signaling pathway activates several different signaling elements, including IRF-3 and NF-κB, which indicate that NTC-Ms (molecule from necrotic tumor cells) could regulate bone marrow development through TRAF-IRF-3-NF-κB pathway and promotes the differentiation of macrophages toward M2-like phenotype. Moreover, NTC-Ms treated TAMs can develop an inhibit phenotype, which expressed Arginase 1, Inducible nitricoxide synthase, interleukin-10, interleukin-12 and induce apoptosis of activated T cells. Supposedly " blocking TLR2/4 activation is inhibited macrophages to key factors of TAM differentiation, tumor immune therapy is a new target ". This paper shows that TLRs and TAM cell differentiation relations and Agaricus blazei Murill polysaccharide promoting tumor immunotherapy mechanism of inhibition macrophage differentiation. Accurate target and further cells, subcellular level of Agaricus blazei Murill polysaccharides inhibited macrophages to mechanism of TAM differentiation. Therefore, blockade of TLR2/4 signaling in local microenvironment should be considered in Agaricus blazei Murill polysaccharide inhibited macrophages to mechanism of TAM differentiation in organ, cell and molecular level, and provide a new way for tumor immunotherapy.