肠道特异性免疫在肠炎癌发生发展中起关键作用，其形成的根本原因是肠道局域免疫细胞对肠道不同菌群及其代谢产物的反应。CARD9-BCL10-MALT1（CBM）信号复合体作为MAPK等炎症信号通路的上游信号，是启动机体对病原菌免疫应答的关键通路。然而，迄今尚不清楚该信号复合体介导抗病原菌免疫应答在肠道肿瘤恶性进程中的作用。我们前期建立了炎症相关结肠肿瘤模型，发现CARD9-/-鼠和MALT1-/-鼠结肠肿瘤较野生鼠加重，而予氟康唑抗真菌治疗能显著缓解肿瘤，特别是MALT1-/-鼠结肠固有层中3型固有淋巴细胞（ILC3）变化极为显著。推测肠道真菌可能通过CBM信号复合体调控ILC3功能，参与结肠肿瘤的发生。本课题拟通过分析结肠肿瘤发生发展中CBM信号复合体调控肠道局域免疫的作用，探讨CBM信号复合体调控ILC3分化和功能的分子机制，为揭示肠道局域免疫影响临床控制结肠肿瘤的免疫治疗提供新理论。

Environmental difference and particularly alimentary customs, which probably affect the commensal microbita, are responsible for the geographical variation in colorectal cancer incidence. Although, the vast majority of studies on commensal microbiota have focused on gut bacteria, recent studies have begun to note the importance of commensal fungi in gut. A rich fungal community that interacts with the immune system was proved in mammalian gut. However, how commensal fungi interacts with immune system and whether this interaction affects colonic tumor development remains unknown. .In our preliminary studies, we found that both CARD9 and MALT1 deficient mice had higher tumor burdens than wide type mice. The number of tumors was decreased after treatment of fluconazole. We also found that the level of ILC3 and production of IL22 was increased in Malt1 knockout mice. Meanwhile, CARD9 knockout mice were both more susceptible to DSS-induced colitis than wild type mice. Based on our preliminary studies, we propose to characterize the molecular mechanism by which CBM signalsome leads to altered immunity to commensal fungi in the gut; to determine how CBM signalsome regulate the function of ILC3 and therefore influence colorectal cancer. .Together, these lines of investigation will reveal molecular mechanism by which host innate immune system affect colonic epithelial homeostasis in response to commensal fungal dysbiosis, which will provide the molecular basis of potential therapeutic targets for designing adjuvant and vaccine against microbial dysbiosis in gut.