肠道粘膜免疫在肿瘤进展中发挥重要作用，结直肠癌局部侵袭与癌旁粘膜免疫抑制微环境密切相关。我们前期研究发现，高分泌IL-10的巨噬细胞在结直肠癌旁粘膜中浸润较多，功能表现为M2型巨噬细胞；CXCL12在癌旁组织中高表达，与M2型巨噬细胞标志物相关；肿瘤来源的IL-6和外泌体促进CXCL12上调。因此，推测肿瘤激活CXCL12/CXCR4通路，促进癌旁粘膜M2型巨噬细胞聚集，进而塑造癌旁免疫抑制微环境，促进结直肠癌局部侵袭，目前具体机制尚未清楚。本研究利用组学、可视化、囊泡递送药物等技术，通过结直肠癌患者标本、原位成瘤小鼠模型和CD11b-Cre/CXCR4fl/fl小鼠模型等，体内外研究M2型巨噬细胞在癌旁粘膜中累积、功能及机制，揭示肠道这一特殊免疫器官与肿瘤进展的关系，探索靶向M2型巨噬细胞控制结直肠癌局部侵袭的新策略，为临床治疗结直肠癌提供新方案。

Mucosal immunity plays a key role in the progression of intestinal tumor. Local invasion of colorectal cancer is highly associated with the immunosuppressive microenvironment in peritumoral intestinal mucosa. Our previous results showed higher accumulation of macrophages secreting IL-10 and functionally tending to be M2 macrophages in peritumoral intestinal mucosa. Higher expression of CXCL12, upregulated by IL-6 and exosomes derived from tumor, in peritumoral intestinal mucosa is correlated with markers of M2 macrophages and would polarize macrophages into M2 macrophages in peritumoral intestinal mucosa. Therefore, we hypothesize that tumor would active CXCL12-CXCR4 signaling pathway to accumulate M2 macrophages and further build immunosuppressive microenvironment in peritumoral intestinal mucosa and promote local invasion of CRC. However, the mechanism of this process is still unclear. This project explores the accumulation, function and mechanism of M2 macrophages in peritumoral microenvironment through analyzing samples from colorectal cancer patients, mouse orthotopic model of colorectal cancer and CD11b-Cre/CXCR4fl/fl mouse model by using RNA-sequencing, atomic force microscope and drug-packaging microparticles and at the same time illuminates relationship of intestinal tract and tumor progression. New therapies targeting macrophages in peritumoral intestinal mucosa and rebuilding peritumoral immune microenvironment will be raised to treat colorectal cancer patients clinically.