AUTHOR=Fan Bohan , Zheng Xin , Wang Yicun , Hu Xiaopeng
TITLE=Predicting prognosis and clinical efficacy of immune checkpoint blockade therapy via interferon-alpha response in muscle-invasive bladder cancer
JOURNAL=Pathology and Oncology Research
VOLUME=29
YEAR=2023
URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2023.1611117
DOI=10.3389/pore.2023.1611117
ISSN=1532-2807
ABSTRACT=Background: Immune checkpoint blockade (ICB) can prompt durable and robust responses in multiple cancers, involving muscle-invasive bladder cancer (MIBC). However, only a limited fraction of patients received clinical benefit. Clarifying the determinants of response and exploring corresponding predictive biomarkers is key to improving outcomes.
Methods: Four independent formerly published cohorts consisting of 641 MIBC patients were enrolled in this study. We first analyzed the associations between various cancer hallmarks and ICB therapy response in two immunotherapeutic cohorts to identify the leading prognostic hallmark in MIBC. Furthermore, advanced machine learning methods were performed to select robust and promising predictors from genes functioning in the above leading pathway. The predictive ability of selected genes was also validated in multiple MIBC cohorts.
Results: We identified and verified IFNα response as the leading cancer hallmark indicating better treatment responses, favorable overall survival, and an inflamed tumor microenvironment with higher infiltration of immune effector cells in MIBC patients treated with ICB therapy. Subsequently, two commonly selected genes, CXCL10 and LAMP3, implied better therapy response and the CXCL10highLAMP3high patients would benefit more from ICB therapy, which was comprehensively validated from the perspective of gene expression, clinical response, patient survival and immune features.
Conclusion: Higher IFNα response primarily predicted better ICB therapeutic responses and reflected an inflamed microenvironment in MIBC. A composite of CXCL10 and LAMP3 expression could serve as promising predictive biomarkers for ICB therapeutic responses and be beneficial for clinical decision-making in MIBC.