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Updated: Jul 11, 2025
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Tumor immune evasion: insights from CRISPR screens and future directions
Tirta Mario Djajawi1,2, Johannes Wichmann3, Stephin J Vervoort3
1Olivia Newton-John Cancer Research Institute, Heidelberg, Vic., Australia.
Abstract:
Despite the clinical success of cancer immunotherapies including immune checkpoint blockade and adoptive cellular therapies across a variety of cancer types, many patients do not respond or ultimately relapse; however, the molecular underpinnings of this are not fully understood. Thus, a system-level understating of the routes to tumor immune evasion is required to inform the design of the next generation of immunotherapy approaches. CRISPR screening approaches have proved extremely powerful in identifying genes that promote tumor immune evasion or sensitize tumor cells to destruction by the immune system. These large-scale efforts have brought to light decades worth of fundamental immunology and have uncovered the key immune-evasion pathways subverted in cancers in an acquired manner in patients receiving immune-modulatory therapies. The comprehensive discovery of the main pathways involved in immune evasion has spurred the development and application of novel immune therapies to target this process. Although successful, conventional CRISPR screening approaches are hampered by a number of limitations, which obfuscate a complete understanding of the precise molecular regulation of immune evasion in cancer. Here, we provide a perspective on screening approaches to interrogate tumor-lymphocyte interactions and their limitations, and discuss further development of technologies to improve such approaches and discovery capability.
Insights
Cancer immunotherapies show promise, but many patients don't respond. Understanding tumor immune evasion pathways is crucial for developing next-generation therapies and improving patient outcomes.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Cancer immunotherapies like immune checkpoint blockade and adoptive cellular therapies have achieved clinical success.
- However, a significant number of patients do not respond or relapse due to a lack of understanding of tumor immune evasion mechanisms.
- A systems-level understanding of tumor immune evasion is needed to design more effective immunotherapies.
Purpose of the Study:
- To provide a perspective on CRISPR screening approaches for interrogating tumor-lymphocyte interactions in cancer.
- To discuss the limitations of current CRISPR screening methods in understanding immune evasion.
- To explore future technological developments for enhancing the discovery of immune evasion pathways.
Main Methods:
- CRISPR screening approaches are powerful tools for identifying genes involved in tumor immune evasion.
- These large-scale genetic screens have elucidated key immune evasion pathways subverted in cancer.
- The study reviews and discusses the application and limitations of these screening technologies.
Main Results:
- CRISPR screens have uncovered fundamental immunology and identified key immune evasion pathways exploited by cancers.
- These discoveries have driven the development of novel immune therapies targeting these evasion processes.
- Despite successes, current screening methods have limitations hindering a complete understanding of molecular regulation.
Conclusions:
- CRISPR screening has significantly advanced the understanding of tumor immune evasion pathways.
- Further technological development is necessary to overcome limitations and improve the discovery of molecular regulators of immune evasion.
- Enhanced screening capabilities will be vital for designing next-generation cancer immunotherapies.
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