Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, London, WC1E 6DD, UK; Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, SE1 9RT, UK.
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, London, WC1E 6DD, UK; Bill Lyons Informatics Centre, University College London Cancer Institute, Paul O'Gorman Building, London, WC1E 6DD, UK.
Semin Cancer Biol. 2022 Sep;84:89-102. doi: 10.1016/j.semcancer.2021.02.013. Epub 2021 Feb 22.
Intratumour heterogeneity (ITH) is pervasive across all cancers studied and may provide the evolving tumour multiple routes to escape immune surveillance. Immune checkpoint inhibitors (CPIs) are rapidly becoming standard of care for many cancers. Here, we discuss recent work investigating the influence of ITH on patient response to immune checkpoint inhibitor (CPI) therapy. At its simplest, ITH may confound the diagnostic accuracy of predictive biomarkers used to stratify patients for CPI therapy. Furthermore, ITH is fuelled by mechanisms of genetic instability that can both engage immune surveillance and drive immune evasion. A greater appreciation of the interplay between ITH and the immune system may hold the key to increasing the proportion of patients experiencing durable responses from CPI therapy.
肿瘤内异质性（ITH）普遍存在于所有研究的癌症中，它可能为不断进化的肿瘤提供了多种逃避免疫监视的途径。免疫检查点抑制剂（CPI）正在迅速成为许多癌症的标准治疗方法。在这里，我们讨论了最近研究 ITH 对患者对免疫检查点抑制剂（CPI）治疗反应的影响的工作。最简单地说，ITH 可能会混淆用于对 CPI 治疗进行分层的预测性生物标志物的诊断准确性。此外，ITH 是由遗传不稳定性机制驱动的，这些机制既可以引发免疫监视，也可以驱动免疫逃逸。更好地了解 ITH 与免疫系统之间的相互作用可能是提高接受 CPI 治疗的患者持久反应比例的关键。
