Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy
Yan Li, Chen Yang, Zhicheng Liu, Shangce Du, Susan Can, Hailin Zhang, Linmeng Zhang, Xiaowen Huang, Zhenyu Xiao, Xiaobo Li, Jing‐Yuan Fang, Wenxin Qin, Chong Sun, Cun Wang, Jun Chen, Huimin Chen
Abstract
BACKGROUND: In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them. METHODS: In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses. RESULTS: We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined. CONCLUSION: Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.