双歧杆菌是肿瘤研究领域极具前景的治疗载体，其免疫原性低，靶向性高，具有一定的免疫调节能力，但其抗肿瘤的分子机制尚不完全明确，抗肿瘤效果仍有待提高,且口服后的体内分布尚存争议。课题组前期构建了白细胞介素-24（IL-24）修饰的短双歧杆菌菌株B.breve-IL24，并证实经尾静脉注射后其具有明显的肿瘤靶向性且抑癌作用强于野生株。为进一步探究口服B.breve-IL24的抑癌作用及分子机制，本项目拟从以下三方面开展：①构建头颈鳞癌荷瘤动物模型，验证口服B.breve-IL24的抑癌作用。②检测口服B.breve-IL24后肿瘤组织的凋亡情况，以及全身和肿瘤微环境中免疫功能的变化。③分析肠道菌群以及双歧杆菌自身对树突状细胞、肠上皮细胞及鳞癌细胞的作用，明确抗肿瘤作用机制；并通过转化远红外蛋白mKate2，实时监测其体内分布。本研究将为双歧杆菌作为肿瘤免疫治疗载体运用于临床提供切实理论依据。

Bifidobacterium, as its low immunogenicity, well targeting and certain immune regulation ability, has become a promising vector for cancer treatment. Bifidobacterium can be used to regulate the immune ability to achieve anti-tumor effect, but the molecular mechanism is still to be perfected. Its anti-tumor effect remains to be improved and the body distribution in oral administration is still controversial.In our previous work, Interleukin-24 transformed Bifidobacterium strain B.breve-IL24 was constructed. It could target the tumor well and its anti-tumor effect was better than the wild type B.breve. Based on this, we intend to make a further exploration on the molecular mechanism of oral administration of B.breve-IL24 in inhibiting cancer, following the methods as below. Firstly, head and neck squamous cell carcinoma cell line was used to construct the tumor-bearing animal model under different immune conditions, and the tumor size was detected to verify the anti-tumor effect. Secondly, the function of immune cells in circulation and tumor tissue, as well as the apoptosis of tumor cells were identified. Thirdly, by analyzing the intestinal microbiome and exploring the effect of B.breve-IL24 on dendritic cells, intestinal epithelial cells and squamous cell, the molecular mechanism of inducing apoptosis and enhancing anti-tumor immunity was clarified. By constructing a strain of Bifidobacterium breve expressing far-infrared protein mKate2, we could monitor its distribution in real time in vivo. Based on the above, we hope to provide a practical basis for the use of Bifidobacterium as a vector for cancer immunotherapy.