ABSTRACT Background Immune cells have been linked to the initiation and progression of tumors, and their presence is often used to predict disease prognosis. However, when it comes to bladder urothelial carcinoma (BLCA), there has not been a comprehensive investigation into the function and prognostic value of different immune cell types. Methods We integrated data from more than 2300 BLCA patients across 14 public datasets. Then we analyzed the quantity of 170 different immune cell signatures using the ssGSEA algorithm. Through meta‐analysis and univariable Cox analysis, we identified prognosis‐associated immune cells and established an immune cell related prognostic signature (IRPS). We then conducted survival analyses to observe the differences in survival across different IRPS‐risk groups. Furthermore, based on the DEGs associated with IRPS, we screened for potential targeted therapeutic agents. Finally, we integrated IRPS with clinical features to establish a comprehensive prognostic index (ICPI). Results Our analysis identified 90 immune cell types that were particularly relevant to BLCA. Then we constructed and validated the IRPS, with high IRPS significantly associated with longer overall survival (HR = 0.73, 95% CI, 0.71–0.76, p < 0.001). In two independent immunotherapy cohorts (IMvigor210 and GSE78220), patients with high IRPS demonstrated significantly prolonged survival following immune checkpoint inhibitor treatment ( p = 0.035, p = 0.019). Several candidate drugs targeting IRPS were identified. The ICPI, developed by integrating IRPS with clinical features, also demonstrated enhanced accuracy in prognostic analysis. Conclusions This study successfully developed and validated a prognostic signature (IRPS) based on comprehensive immune cell infiltration analysis, along with its integrated index (ICPI). IRPS/ICPI serves as an effective tool for predicting BLCA patient prognosis and guiding immunotherapy strategies, while also aiding in the identification of patient populations likely to benefit from immunotherapy.
Yan et al. (2026) studied this question.