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Updated: Oct 8, 2025
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy
Yan Li1,2, Chen Yang3, Zhicheng Liu4
1State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, 200001, China.
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.
Insights
This study aggregated functional genetic screens to identify 105 genes regulating tumor immunity. MON2 was found to be a novel target, and a CRISPR screening-based tumor-intrinsic immune score (CTIS) was developed to predict immunotherapy response.
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- Functional genetic screens identify regulators of tumor-immune interactions.
- Systematic aggregation and analysis of existing screen data are limited.
Purpose of the Study:
- To systematically collect and analyze functional genetic screens in tumor immunity.
- To identify novel regulators and therapeutic targets in immuno-oncology.
- To develop a predictive signature for immunotherapy response.
Main Methods:
- Comprehensive data collection of tumor immunity-associated functional screens.
- Integrative analysis of large-scale genomic datasets.
- Identification of regulator genes mediating tumor elimination sensitivity/resistance.
Main Results:
- Identified 105 regulator genes impacting immune cell-induced tumor elimination.
- Discovered MON2 as a novel immuno-oncology target with therapeutic potential.
- Developed the CTIS signature for predicting response to immune checkpoint blockade (ICB) and immunomodulatory agents.
Conclusions:
- Findings offer insights into immuno-oncology mechanisms.
- Novel opportunities for enhancing current immunotherapy efficacy are presented.
- Identified MON2 and CTIS as valuable tools for immuno-oncology research and treatment.
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