Multiple cell-signalling pathways converge on chromatin to induce gene expression programmes. The inducible transcriptional programmes that are established as a result of inflammatory or oncogenic signals are controlled by shared chromatin regulators. Therapeutic targeting of such chromatin dependencies has proved effective for controlling tumorigenesis and for preventing immunopathologies that are driven by overt inflammation. In this Review, we discuss how chromatin dependencies are established to regulate the expression of key oncogenes and inflammation-promoting genes and how a better mechanistic understanding of such chromatin dependencies can be leveraged to improve the magnitude, timing, duration and selectivity of cell responses with the aim of minimizing unwanted cellular and systemic effects. Recently, exciting progress has been made in cancer immunotherapy and in the development of drugs that target chromatin regulators. We discuss recent advances in clinical trials and the challenge of combining immune-cell-based therapies and epigenetic therapies to improve human health.

多种细胞信号通路在染色质上汇聚，以诱导基因表达程序。由于炎症或致癌信号而建立的诱导型转录程序由共享的染色质调节剂控制。已经证明了针对这种染色质依赖性的治疗靶标对于控制肿瘤发生和预防由明显炎症驱动的免疫病理学是有效的。在这篇综述中，我们讨论了如何建立染色质依赖性来调节关键癌基因和促炎基因的表达，以及如何利用对此类染色质依赖性的更好的机械理解来改善细胞应答的幅度，时间，持续时间和选择性。目的是最大程度地减少不必要的细胞和全身作用。最近，在癌症免疫治疗和靶向染色质调节剂的药物开发方面已经取得了令人兴奋的进展。我们讨论了临床试验的最新进展以及将基于免疫细胞的疗法与表观遗传疗法相结合以改善人类健康的挑战。