Advancements in CRISPR screens for the development of cancer immunotherapy strategies

Yan-Ruide Li; Zibai Lyu; Yanxin Tian; Ying Fang; Yichen Zhu; Yuning Chen; Lili Yang

doi:10.1016/j.omto.2023.100733

Advancements in CRISPR screens for the development of cancer immunotherapy strategies

Mol Ther Oncolytics. 2023 Oct 5:31:100733. doi: 10.1016/j.omto.2023.100733. eCollection 2023 Dec 19.

Authors

Yan-Ruide Li¹, Zibai Lyu¹, Yanxin Tian¹, Ying Fang¹, Yichen Zhu¹, Yuning Chen¹, Lili Yang^{1

2

3

4}

Affiliations

¹ Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

CRISPR screen technology enables systematic and scalable interrogation of gene function by using the CRISPR-Cas9 system to perturb gene expression. In the field of cancer immunotherapy, this technology has empowered the discovery of genes, biomarkers, and pathways that regulate tumor development and progression, immune reactivity, and the effectiveness of immunotherapeutic interventions. By conducting large-scale genetic screens, researchers have successfully identified novel targets to impede tumor growth, enhance anti-tumor immune responses, and surmount immunosuppression within the tumor microenvironment (TME). Here, we present an overview of CRISPR screens conducted in tumor cells for the purpose of identifying novel therapeutic targets. We also explore the application of CRISPR screens in immune cells to propel the advancement of cell-based therapies, encompassing T cells, natural killer cells, dendritic cells, and macrophages. Furthermore, we outline the crucial components necessary for the successful implementation of immune-specific CRISPR screens and explore potential directions for future research.

Keywords: NK cells; T cells; cancer immunotherapy; chimeric antigen receptor (CAR)-engineered T (CAR-T) cells; clustered regularly interspaced short palindromic repeats (CRISPR) screen; gene discovery; genetic engineering; tumor immunology.

Publication types

Review