免疫治疗在微卫星稳定类型（microsatellite stable status, MSS）的晚期结直肠癌中疗效较差，但机制不明。一些研究显示肠道微生物及肿瘤相关巨噬细胞可以通过影响肿瘤的免疫微环境进而影响免疫治疗效果。我们前期预实验发现，在MSS型的晚期结直肠癌中，具核梭杆菌与免疫抑制存在显著的临床相关性，且与肿瘤相关巨噬细胞M2型极化有关。基于进一步的研究结果我们提出假设：具核梭杆菌可能通过激活NF-κB/IL-6/STAT3信号通路诱导肿瘤相关巨噬细胞M2极化促进结直肠癌免疫抑制微环境的形成。本课题拟在前期研究基础之上通过体内外实验论证该假设。本研究有望为提高MSS型晚期结直肠癌的免疫疗效提供新策略和新靶点。

The immunotherapeutic effect for advanced colorectal cancer with microsatellite stable status (MSS) is poor, but the mechanism involved is still unknown. Some studies have shown that gut microbiome and tumor-associated macrophages may affect the immunotherapeutic effect for cancers by affecting the tumor immune microenvironment. Based on previous studies, we found that Fusobacterium nucleatum was clinically correlated with immunosuppression and M2 polarization of tumor-associated macrophages in advanced colorectal cancer with MSS. Furthermore, we proposed the hypothesis that Fusobacterium nucleatum may induce M2 polarization of tumor-associated macrophages by activating the NF-κB / IL-6 / STAT3 signaling pathway to promote the formation of immunosuppressive microenvironment in colorectal cancer. Next, this study plans to test this hypothesis through in vivo and in vitro experiments based on previous research. This project is expected to provide new strategies and new targets for improving immunotherapeutic effect for advanced colorectal cancer with MSS.