{"title":"抑制TFF3通过下调结直肠癌中PD-L1的表达改善CD8+ T细胞的浸润和功能。","authors":"Xiaoxue Pan, Jichang Li, Jing Zhu, Xin Wang, Yucun Liu, Shanwen Chen, Pengyuan Wang","doi":"10.1007/s00384-025-04964-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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<sup>+</sup> T cells in colorectal tumor tissues.</p><p><strong>Methods: </strong>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<sup>+</sup> 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.</p><p><strong>Results: </strong>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<sup>+</sup> T cells.</p><p><strong>Conclusion: </strong>Knockdown of TFF3 improved the infiltration of CD8<sup>+</sup> T cells and anti-tumor capabilities.</p>","PeriodicalId":13789,"journal":{"name":"International Journal of Colorectal Disease","volume":"40 1","pages":"170"},"PeriodicalIF":2.3000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325462/pdf/","citationCount":"0","resultStr":"{\"title\":\"Inhibition of TFF3 improves the infiltration and function of CD8<sup>+</sup> T cells by downregulating the expression of PD-L1 in colorectal cancer.\",\"authors\":\"Xiaoxue Pan, Jichang Li, Jing Zhu, Xin Wang, Yucun Liu, Shanwen Chen, Pengyuan Wang\",\"doi\":\"10.1007/s00384-025-04964-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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<sup>+</sup> T cells in colorectal tumor tissues.</p><p><strong>Methods: </strong>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<sup>+</sup> 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.</p><p><strong>Results: </strong>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<sup>+</sup> T cells.</p><p><strong>Conclusion: </strong>Knockdown of TFF3 improved the infiltration of CD8<sup>+</sup> T cells and anti-tumor capabilities.</p>\",\"PeriodicalId\":13789,\"journal\":{\"name\":\"International Journal of Colorectal Disease\",\"volume\":\"40 1\",\"pages\":\"170\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325462/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Colorectal Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00384-025-04964-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Colorectal Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00384-025-04964-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Inhibition of TFF3 improves the infiltration and function of CD8+ T cells by downregulating the expression of PD-L1 in colorectal cancer.
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.
期刊介绍：
The International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery aims to publish novel and state-of-the-art papers which deal with the physiology and pathophysiology of diseases involving the entire gastrointestinal tract. In addition to original research articles, the following categories will be included: reviews (usually commissioned but may also be submitted), case reports, letters to the editor, and protocols on clinical studies.
The journal offers its readers an interdisciplinary forum for clinical science and molecular research related to gastrointestinal disease.
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