Machine learning-based identification of tumor-infiltrating immune cell-associated model with appealing implications in improving prognosis and immunotherapy response in bladder cancer patients

Frontiers in Immunology

Immunology

Zhigang Ji¹  Hualin Chen¹  Wenjie Yang¹ 

[1] Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;

关键词: immunotherapy;    bladder cancer;    immune checkpoint;    immune infiltration;    prognosis;    machine learning;   

DOI  :  10.3389/fimmu.2023.1171420

 received in 2023-02-22, accepted in 2023-03-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundImmune cells are crucial components of the tumor microenvironment (TME) and regulate cancer cell development. Nevertheless, the clinical implications of immune cell infiltration-related mRNAs for bladder cancer (BCa) are still unclear.MethodsA 10-fold cross-validation framework with 101 combinations of 10 machine-learning algorithms was employed to develop a consensus immune cell infiltration-related signature (IRS). The predictive performance of IRS in terms of prognosis and immunotherapy was comprehensively evaluated.ResultsThe IRS demonstrated high accuracy and stable performance in prognosis prediction across multiple datasets including TCGA-BLCA, eight independent GEO datasets, our in-house cohort (PUMCH_Uro), and thirteen immune checkpoint inhibitors (ICIs) cohorts. Additionally, IRS was superior to traditional clinicopathological features (e.g., stage and grade) and 94 published signatures. Furthermore, IRS was an independent risk factor for overall survival in TCGA-BLCA and several GEO datasets, and for recurrence-free survival in PUMCH_Uro. In the PUMCH_Uro cohort, patients in the high-IRS group were characterized by upregulated CD8A and PD-L1 and TME of inflamed and immunosuppressive phenotypes. As predicted, these patients should benefit from ICI therapy and chemotherapy. Furthermore, in the ICI cohorts, the high-IRS group was related to a favorable prognosis and responders have dramatically higher IRS compared to non-responders.ConclusionsGenerally, these indicators suggested the promising application of IRS in urological practices for the early identification of high-risk patients and potential candidates for ICI application to prolong the survival of individual BCa patients.

【 授权许可】

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Copyright © 2023 Chen, Yang and Ji