Taylor Erin M, Koss Brian, Davis Lauren E, Tackett Alan J
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Methods Mol Biol. 2020;2055:213-228. doi: 10.1007/978-1-4939-9773-2_10.
Recent advances in immunotherapy have revolutionized the treatment of certain cancers. Some patients show a durable response to these immunotherapies, while others show little benefit or develop resistance. Identification of biomarkers to predict responsiveness will be helpful for informing treatment strategies; and would furthermore lead to the identification of molecular pathways dysregulated in nonresponding patients that could be targeted for therapeutic development. Pathways of epigenetic modification, such as histone posttranslational modifications (PTMs), have been shown to be dysregulated in certain cancer and immune cells. Histones are abundant cellular proteins readily assayed with high-throughput technologies, making them attractive targets as biomarkers. We explore promising advancements for using histone PTMs as immunotherapy responsiveness biomarkers in both cancer and immune cells, and provide a methodological workflow for assaying histone PTMs in relevant samples.
免疫疗法的最新进展彻底改变了某些癌症的治疗方式。一些患者对这些免疫疗法表现出持久的反应,而另一些患者则获益甚微或产生耐药性。识别预测反应性的生物标志物将有助于制定治疗策略;此外,还将有助于识别无反应患者中失调的分子途径,这些途径可作为治疗开发的靶点。表观遗传修饰途径,如组蛋白翻译后修饰(PTM),已被证明在某些癌症和免疫细胞中失调。组蛋白是丰富的细胞蛋白,易于通过高通量技术进行检测,使其成为有吸引力的生物标志物靶点。我们探讨了将组蛋白PTM用作癌症和免疫细胞中免疫疗法反应性生物标志物的有前景的进展,并提供了在相关样本中检测组蛋白PTM的方法流程。