Multi-omics indicators of long-term survival benefits after immune checkpoint inhibitor therapy

免疫检查点抑制剂治疗后长期生存获益的多组学指标

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作者:Jie Zhao, Yiting Dong, Hua Bai, Fan Bai, Xiaoyan Yan, Jianchun Duan, Rui Wan, Jiachen Xu, Kailun Fei, Jie Wang, Zhijie Wang

Abstract

Molecular indicators of long-term survival (LTS) in response to immune-checkpoint inhibitor (ICI) treatment have the potential to provide both mechanistic and therapeutic insights. In this study, we construct predictive models of LTS following ICI therapy based on data from 158 clinical trials involving 21,023 patients of 25 cancer types with available 1-year overall survival (OS) rates. We present evidence for the use of 1-year OS rate as a surrogate for LTS. Based on these and corresponding TCGA multi-omics data, total neoantigen, metabolism score, CD8+ T cell, and MHC_score were identified as predictive biomarkers. These were integrated into a Gaussian process regression model that estimates "long-term survival predictive score of immunotherapy" (iLSPS). We found that iLSPS outperformed the predictive capabilities of individual biomarkers and successfully predicted LTS of patient groups with melanoma and lung cancer. Our study explores the feasibility of modeling LTS based on multi-omics indicators and machine-learning methods.

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