CRISPR/Cas9 system: recent applications in immuno-oncology and cancer immunotherapy

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is essentially an adaptive immunity weapon in prokaryotes against foreign DNA. This system inspires the development of genome-editing technology in eukaryotes. In biomedicine research, CRISPR has offered a powerful platform to establish tumor-bearing models and screen potential targets in the immuno-oncology field, broadening our insights into cancer genomics. In translational medicine, the versatile CRISPR/Cas9 system exhibits immense potential to break the current limitations of cancer immunotherapy, thereby expanding the feasibility of adoptive cell therapy (ACT) in treating solid tumors. Herein, we first explain the principles of CRISPR/Cas9 genome editing technology and introduce CRISPR as a tool in tumor modeling. We next focus on the CRISPR screening for target discovery that reveals tumorigenesis, immune evasion, and drug resistance mechanisms. Moreover, we discuss the recent breakthroughs of genetically modified ACT using CRISPR/Cas9. Finally, we present potential challenges and perspectives in basic research and clinical translation of CRISPR/Cas9. This review provides a comprehensive overview of CRISPR/Cas9 applications that advance our insights into tumor-immune interaction and lay the foundation to optimize cancer immunotherapy.