Targeting alternative splicing in cancer immunotherapy

Nan Han; Zhaoqi Liu

doi:10.3389/fcell.2023.1232146

Targeting alternative splicing in cancer immunotherapy

Front Cell Dev Biol. 2023 Aug 10:11:1232146. doi: 10.3389/fcell.2023.1232146. eCollection 2023.

Authors

Nan Han^{1

2}, Zhaoqi Liu^{1

2}

Affiliations

¹ Chinese Academy of Sciences Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
² University of Chinese Academy of Sciences, Beijing, China.

Abstract

Tumor immunotherapy has made great progress in cancer treatment but still faces several challenges, such as a limited number of targetable antigens and varying responses among patients. Alternative splicing (AS) is an essential process for the maturation of nearly all mammalian mRNAs. Recent studies show that AS contributes to expanding cancer-specific antigens and modulating immunogenicity, making it a promising solution to the above challenges. The organoid technology preserves the individual immune microenvironment and reduces the time/economic costs of the experiment model, facilitating the development of splicing-based immunotherapy. Here, we summarize three critical roles of AS in immunotherapy: resources for generating neoantigens, targets for immune-therapeutic modulation, and biomarkers to guide immunotherapy options. Subsequently, we highlight the benefits of adopting organoids to develop AS-based immunotherapies. Finally, we discuss the current challenges in studying AS-based immunotherapy in terms of existing bioinformatics algorithms and biological technologies.

Keywords: alternative splicing; cancer; immunotherapy; organoid; precision medicine.

Publication types

Review

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant 32170565), National Key R&D Program of China (grant 2022YFC2704202), the Beijing Natural Science Foundation (grant Z200023) and the CAS Hundred Talents Program.