抑制三叶因子3（TFF3）可通过下调结直肠癌中程序性死亡受体配体1（PD-L1）的表达来改善CD8 T细胞的浸润和功能。
Inhibition of TFF3 improves the infiltration and function of CD8 T cells by downregulating the expression of PD-L1 in colorectal cancer.
作者信息
Pan Xiaoxue, Li Jichang, Zhu Jing, Wang Xin, Liu Yucun, Chen Shanwen, Wang Pengyuan
机构信息
Department of Gastrointestinal Surgery, Peking University First Hospital, Beijing, 100034, China.
出版信息
Int J Colorectal Dis. 2025 Aug 5;40(1):170. doi: 10.1007/s00384-025-04964-0.
BACKGROUND
Colorectal cancer is a common malignant tumor of the digestive tract with a high mortality rate. TFF3 is a secreted protein expressed in various cancers. The aim of the study is to report that inhibiting TFF3 increases the function and infiltration of CD8 T cells in colorectal tumor tissues.
METHODS
The proteomics analysis confirmed the high expression of secreted TFF3 in the supernatant of colorectal cancer cells, and databases were used to analyze the immune infiltration in tumor tissues. qPCR test was used to demonstrate the high levels of secreted TFF3 affecting the function of CD8 T cells. In vivo experiments were used to observe the effects of TFF3 knockdown on tumor growth and immune cell infiltration. Tumor-infiltrating T lymphocytes were sorted for RNA sequencing and mechanism explanation.
RESULTS
Inhibiting the expression of TFF3 in tumor tissues improved immune cell infiltration and enhanced anti-tumor effects. TFF3 knockdown downregulated the expression of PD-L1 in tumor tissues through the AKT/mTOR pathway, which enhanced the function of CD8 T cells.
CONCLUSION
Knockdown of TFF3 improved the infiltration of CD8 T cells and anti-tumor capabilities.
背景
结直肠癌是一种常见的消化道恶性肿瘤，死亡率很高。三叶因子3（TFF3）是一种在多种癌症中表达的分泌蛋白。本研究的目的是报告抑制TFF3可增强结直肠肿瘤组织中CD8 T细胞的功能和浸润。
方法
蛋白质组学分析证实结直肠癌细胞上清液中分泌型TFF3高表达，并利用数据库分析肿瘤组织中的免疫浸润情况。采用qPCR检测来证明高水平分泌型TFF3对CD8 T细胞功能的影响。体内实验用于观察TFF3基因敲低对肿瘤生长和免疫细胞浸润的影响。对肿瘤浸润性T淋巴细胞进行分选以进行RNA测序和机制解释。
结果
抑制肿瘤组织中TFF3的表达可改善免疫细胞浸润并增强抗肿瘤作用。TFF3基因敲低通过AKT/mTOR途径下调肿瘤组织中PD-L1的表达，从而增强CD8 T细胞的功能。
结论
敲低TFF3可改善CD8 T细胞的浸润和抗肿瘤能力。
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