Integrative analysis of T cell-mediated tumor killing-related genes reveals KIF11 as a novel therapeutic target in esophageal squamous cell carcinoma

• DOI: 10.1186/s12967-025-06178-y
• Publication Date: 2025-02-18T12:00:32Z
• Authors: Xinxin Cheng; Huihui Zhao; Zhangwang Li; Liping Yan; Qingjie Min; Qingnan Wu; Qimin Zhan
• Keywords: ESCC; Prognostic signature; R; Medicine; Immunotherapy; T cell-mediated tumor killing; KIF11

Immune checkpoint inhibitors (ICIs) are emerging promising agents for the treatment of patients with esophageal squamous cell carcinoma (ESCC), however, there only a small proportion respond to ICI therapy. Therefore, selecting candidate who will benefit most from these drugs is critical. However, validated biomarkers predicting immunotherapy response and overall survival lacking. As fundamental principle therapy T cell-mediated tumor killing (TTK), we aimed develop unique TTK-related gene prognostic index (TTKPI) outcomes responses immune-based in ESCC patients. Transcriptomic clinical information were GSE53625, GSE53624, GSE47404 TCGA datasets. genes TISIDB database. The LASSO Cox regression model was employed create TTKPI. prediction potential TTKPI evaluated using KM curve time-dependent ROC analysis. Finally, relationship between efficacy investigated trials ICIs (GSE91061, GSE135222, IMvigor210 cohort). role KIF11 accelerating progression via variety functional experiments, including western blot, CCK-8, colony formation, wound healing scratch, xenograft model. expression detected by multiplex fluorescent immunohistochemistry on tissue microarray We constructed based 8 genes. low-risk exhibited better survival. significantly positively correlated main immune molecules levels. Furthermore, more prone reap benefits cohort undergoing anti-PD-L1 Moreover, performed experiments KIF11, which ranked as significant risk among Our findings identified that knockdown hindered proliferation mobility cells. negatively related CD8+ infiltration patient samples. biomarker accurately determining effectiveness This indicator can help receive timely precise early intervention, thereby advancing personalized medicine facilitating immuno-oncology research. plays crucial driving migration may act ESCC.