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基因融合新抗原:癌症免疫治疗的新兴靶点。

Gene fusion neoantigens: Emerging targets for cancer immunotherapy.

机构信息

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.

出版信息

Cancer Lett. 2021 May 28;506:45-54. doi: 10.1016/j.canlet.2021.02.023. Epub 2021 Mar 4.

Abstract

Tumor neoantigens play an important role in current cancer immunotherapies. The most commonly studied class of tumor neoantigens contains those derived from single-nucleotide variants (SNVs) and insertions or deletions (Indels). However, gene fusions are also ideal sources of tumor neoantigens, as they can form new open reading frames (ORFs). Compared with SNV and Indel (SNV&Indel) neoantigens, fusion gene neoantigens tend to be more immunogenic, have more targets per mutation, and are more broadly shared across different cancer types. As a result, they are an important class of tumor neoantigens and emerging targets for cancer immunotherapies, with uses as prognostic biomarkers of immune checkpoint blockade (ICB) and in the development of tumor vaccines, adoptive cell therapies and tumor immune microenvironment modulation. In this review, we introduce the chromosomal basis and characteristics of gene fusions. Then, we summarize the predictive tools, mutation burden and immunogenicity of gene fusion neoantigens. Further, we discuss applications and future improvements of gene fusion neoantigens with respect to current cancer immunotherapies and novel developments in cancer treatment.

摘要

肿瘤新生抗原在当前的癌症免疫疗法中发挥着重要作用。最常研究的一类肿瘤新生抗原包含源自单核苷酸变异(SNV)和插入或缺失(Indel)的抗原。然而,基因融合也是肿瘤新生抗原的理想来源,因为它们可以形成新的开放阅读框(ORFs)。与 SNV 和 Indel(SNV&Indel)新生抗原相比,融合基因新生抗原往往更具免疫原性,每个突变的靶点更多,在不同癌症类型中更广泛共享。因此,它们是一类重要的肿瘤新生抗原,也是癌症免疫疗法的新兴靶点,可作为免疫检查点阻断(ICB)的预后生物标志物,并用于开发肿瘤疫苗、过继细胞疗法和肿瘤免疫微环境调节。在这篇综述中,我们介绍了基因融合的染色体基础和特征。然后,我们总结了基因融合新生抗原的预测工具、突变负担和免疫原性。此外,我们还讨论了基因融合新生抗原在当前癌症免疫疗法以及癌症治疗的新进展中的应用和未来改进。

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