PDF(Pubmed)
Abstract：
Immune checkpoint inhibitors (ICIs) demonstrate durable responses, long-term survival benefits, and improved outcomes in cancer patients compared to chemotherapy. However, the majority of cancer patients do not respond to ICIs, and a high proportion of those patients who do respond to ICI therapy develop innate or acquired resistance to ICIs, limiting their clinical utility. The most studied predictive tissue biomarkers for ICI response are PD-L1 immunohistochemical expression, DNA mismatch repair deficiency, and tumour mutation burden, although these are weak predictors of ICI response. The identification of better predictive biomarkers remains an important goal to improve the identification of patients who would benefit from ICIs. Here, we review established and emerging biomarkers of ICI response, focusing on epigenomic and genomic alterations in cancer patients, which have the potential to help guide single-agent ICI immunotherapy or ICI immunotherapy in combination with other ICI immunotherapies or agents. We briefly review the current status of ICI response biomarkers, including investigational biomarkers, and we present insights into several emerging and promising epigenomic biomarker candidates, including current knowledge gaps in the context of ICI immunotherapy response in melanoma patients.
摘要：
免疫检查点抑制剂(ICIs)表现出持久的反应，长期生存益处，与化疗相比，癌症患者的预后有所改善。然而,大多数癌症患者对ICI没有反应，对ICI治疗有反应的患者中有很大比例会对ICI产生先天或后天的耐药性，限制其临床效用。研究最多的ICI反应的预测组织生物标志物是PD-L1免疫组织化学表达，DNA错配修复缺陷,和肿瘤突变负担，尽管这些是ICI反应的弱预测因子。更好的预测性生物标志物的鉴定仍然是改善将受益于ICI的患者的鉴定的重要目标。这里,我们回顾了ICI反应的已建立和新兴的生物标志物，关注癌症患者的表观基因组和基因组改变，它们有可能帮助指导单药ICI免疫治疗或ICI免疫治疗与其他ICI免疫治疗或药物的组合。我们简要回顾了ICI反应生物标志物的现状，包括研究性生物标志物，我们提出了一些新兴的和有前途的表观基因组生物标志物候选的见解，包括目前在黑色素瘤患者ICI免疫治疗反应方面的知识差距。
