An evaluation of the tumor microenvironment through CALR, IL1R1, IFNB1, and IFNG to assess prognosis and immunotherapy response in bladder cancer patients.

Liu, Lilong; Liu, Zhenghao; Fan, Lei; Yao, Zhipeng; Hu, Junyi; Hou, Yaxin; Li, Yang; Ding, Yuhong et al. · Elife · 2025

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Abstract

Immunogenic cell death (ICD) is a type of cell death sparking adaptive immune responses that can reshape the tumor microenvironment. Exploring key ICD-related genes in bladder cancer (BLCA) could enhance personalized treatment. The Cancer Genome Atlas (TCGA) BLCA patients were divided into two ICD subtypes: ICD-high and ICD-low. High ICD expression linked to increased immune cell infiltration and longer survival, but with potentially suppressed immune function. The high ICD group responded better to PD1-targeted therapy. A risk-scoring model with four ICD-related genes (CALR, IL1R1, IFNB1, IFNG) was validated across TCGA, GEO datasets, and tissue samples, showing higher risk score correlated with weaker anti-tumor immune function, more tumor-promoting elements, lower immunotherapy response rates, and shorter patient survival. This study connects ICD-related genes to BLCA prognosis and immune infiltration, offering a vital tool for personalized treatment guidance.

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