MYC 与多种人类肿瘤的发病机制有关，多年来一直被描述为一种转录因子，可调节具有多效性功能的基因，以促进致瘤性生长。然而，尽管人们付出了巨大的努力来确定 MYC 的特定靶基因（仅能促进肿瘤发生），但该领域尚未就这是否是 MYC 的关键功能达成共识。最近的工作将 MYC 功能的观点从基因特异性转录因子转变为重要的应激恢复因子。在高度增殖的细胞中，MYC 通过促进核心启动子处的 DNA 修复、保护停滞的复制叉和/或防止转录复制冲突来保持细胞完整性。此外，越来越多的证据表明，MYC不仅通过驱动细胞自主生长来促进肿瘤发生，而且还使肿瘤能够逃避宿主的免疫系统。在这篇综述中，我们总结了目前对 MYC 如何损害抗肿瘤免疫的理解，以及为什么这种功能在进化上与 MYC 蛋白家族的生物学密切相关。我们展示了为什么 MYC 的细胞自主功能和免疫逃避功能是相互依赖的，并讨论了在癌症治疗中靶向 MYC 蛋白的方法。© 2024 作者。约翰·威利出版的《分子肿瘤学》

MYC has been implicated in the pathogenesis of a wide range of human tumors and has been described for many years as a transcription factor that regulates genes with pleiotropic functions to promote tumorigenic growth. However, despite extensive efforts to identify specific target genes of MYC that alone could be responsible for promoting tumorigenesis, the field is yet to reach a consensus whether this is the crucial function of MYC. Recent work shifts the view on MYC's function from being a gene-specific transcription factor to an essential stress resilience factor. In highly proliferating cells, MYC preserves cell integrity by promoting DNA repair at core promoters, protecting stalled replication forks, and/or preventing transcription-replication conflicts. Furthermore, an increasing body of evidence demonstrates that MYC not only promotes tumorigenesis by driving cell-autonomous growth, but also enables tumors to evade the host's immune system. In this review, we summarize our current understanding of how MYC impairs antitumor immunity and why this function is evolutionarily hard-wired to the biology of the MYC protein family. We show why the cell-autonomous and immune evasive functions of MYC are mutually dependent and discuss ways to target MYC proteins in cancer therapy.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.