IRnet: Immunotherapy response prediction using pathway knowledge-informed graph neural network

Abstract

IntroductionImmune checkpoint inhibitors (ICIs) are potent and precise therapies for various cancer types, significantly improving survival rates in patients who respond positively to them. However, only a minority of patients benefit from ICI treatments. ObjectivesIdentifying ICI responders before treatment could greatly conserve medical resources, minimize potential drug side effects, and expedite the search for alternative therapies. Our goal is to introduce a novel deep-learning method to predict ICI treatment responses in cancer patients. MethodsThe proposed deep-learning framework leverages graph neural network and biological pathway knowledge. We trained and tested our method using ICI-treated patients’ data from several clinical trials covering melanoma, gastric cancer, and bladder cancer. ResultsOur results demonstrate that this predictive model outperforms current state-of-the-art methods and tumor microenvironment-based predictors. Additionally, the model quantifies the importance of pathways, pathway interactions, and genes in its predictions. A web server for IRnet has been developed and deployed, providing broad accessibility to users at https://irnet.missouri.edu. ConclusionIRnet is a competitive tool for predicting patient responses to immunotherapy, specifically ICIs. Its interpretability also offers valuable insights into the mechanisms underlying ICI treatments.