中医理论认为，结直肠癌属癥瘕范畴。其病机为“正气亏虚，毒瘀内结”。具有扶正活血解毒法的芪贞汤对该病疗效确切，但作用机制尚不十分明确。PD-1抗体是结直肠癌免疫治疗的重要药物，但其具有应答率较低的问题。有文献报道，肠道益生菌艾克曼可诱导巨噬细胞向M1型转化和DC细胞成熟，继而通过IL-12/JAK-STAT通路发挥对PD-1抗体的增敏作用。本课题组研究发现，用芪贞汤灌胃对结直肠癌模型小鼠治疗有明显的疗效，并能够显著提高小鼠肠道艾克曼菌丰度。据此提出“芪贞汤通过提高肠道艾克曼菌丰度激活免疫反应治疗结直肠癌；而且其激活的免疫反应可以通过进一步增敏PD-1抗体发挥辅助免疫治疗的作用”的研究假说。拟在体内外研究芪贞汤通过益生菌艾克曼产生的免疫应答,以及这些免疫应答细胞和分子对PD-1抗体的增敏效应的作用和分子机制。为中医药治疗结直肠癌和辅助免疫治疗的作用提供新的理论基础。

According to the fundamental theory of traditional Chinese medicine, colorectal cancer belongs to abdominal masses, ontologically. Its pathogenesis is explained as “stagnation of zheng qi, and stagnant toxins in body”. The traditional Chinese herbal decoction QiZhen can strengthen the body’s immunity, remove toxins and activate blood circulation is effective in suporting the treatment of colorectal cancer, but the mechanism of action is not yet clear. PD-1 antibody is an important drug for immunotherapy of colorectal cancer, but it has the problem of lower response rate. It has been reported that the intestinal probiotic A.muciniphila can induce the transformation of macrophages into M1 type and mature to DC cells, and then sensitize PD-1 antibody through IL-12/JAK-STAT pathway .Our research group found that the treatment of colorectal cancer model mice by QiZhen decoction has an obvious curative effect, and it can also improve the abundance of A.muciniphila in mice significantly. Based on this finding, we propose that QiZhen decoction can treat colorectal cancer by improving the abundance of intestinal A.muciniphila to activate the immune response; and it can play a role in adjuvant immunotherapy by further sensitizing PD-1 antibody. We intended to study the immune response of QiZhen decoction that is produced by A.muciniphila in vitro and in vivo, and the effect and molecular mechanism of the related immune response cells and molecules on the sensitizing effect of PD-1 antibodies. It can provide a new theoretical basis for the effect of traditional Chinese medicine in the treatment of colorectal cancer and adjuvant immunotherapy.