肿瘤免疫疗法在癌症治疗方面取得了巨大的进展，但仍面临几个挑战，如可靶向抗原的数量有限和不同患者的反应不同。剪接异构体在几乎所有哺乳动物mRNA成熟过程中都起着重要作用。最近的研究表明，剪接异构体有助于扩展癌症特异性抗原和调节免疫原性，因此成为解决上述挑战的有希望的解决方案。器官样培养技术可以保留个体免疫微环境并降低实验模型的时间/经济成本，促进基于剪接的免疫疗法的发展。在此，我们总结了剪接在免疫疗法中的三个关键作用：产生新型抗原的资源，免疫治疗调控的靶点以及指导免疫疗法选择的生物标记物。随后，我们强调采用器官样培养体开发基于剪接的免疫疗法的优势。最后，我们讨论了在现有生物信息学算法和生物技术方面研究基于剪接的免疫疗法的当前挑战。版权所有 © 2023 Han and Liu.

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.Copyright © 2023 Han and Liu.