M1/M2型巨噬细胞分化平衡是调节肿瘤细胞微环境的重要因素，重塑其平衡可以提高机体自身对肿瘤细胞的免疫反应，同时也增强了药物疗效。但目前对于调控M1/M2型巨噬细胞分化平衡的机制仍不清楚。我们前期工作证实了干扰素调节因子（IRF8）能重塑结肠肿瘤微环境中M1/M2型巨噬细胞表型，通过释放IL-28B，绑定肿瘤细胞表面IL-10R2受体，促进肿瘤细胞凋亡和抑制肿瘤细胞转移。在此项目中，我们将进一步结合AOM/DSS诱导特异性巨噬细胞IRF8-/-小鼠的结肠肿瘤模型，阐明IRF8缺失对肿瘤内巨噬细胞分化、肿瘤微环境中细胞毒性T和CD4T辅助细胞的影响；在体内外证明IL-28B/IL-10R2调节肠肿瘤细胞生物学行为的分子机制，为结肠肿瘤的靶向治疗提供理论基础和实验依据。

The balance of type M1/M2 Macrophage was an important role of tumor microenvironment (TME) for tumor growth and development. The studies suggested that reprograming macrophage phenotype could enhance the host self-immune response to tumor cells and strength the drug effect. But the mechanism of reprograming macrophage phenotype was still unclear. Our previous results indicated that.Interferon regulatory factor 8 (IRF8) could regulate the type M1/M2 macrophage differentiation in colorectal cancer, and release IL-28B, binding to the IL-10R2 of tumor cell membrane surface, which promote the apoptosis and metastasis of tumor cells. In current project, we will confirm whether IRF8 deficiency results to the inter-tumor macrophage differentiation, the proportion of cytotoxic T cells and CD4 T helper cells in TME by generating the colon cancer model with the conditional macrophage IRF8-/- mice induced by AOM/DSS. We also verify the mechanism of IL-28B/IL-10R2 signal pathway aiming to tumor biology. And thoes researches will provide theoretical foundation and experimental basis for the targeted therapy of colorectal cancer.