Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, Level 2, 3A Symonds Street, Auckland 1010, New Zealand.
Int J Mol Sci. 2024 Jun 30;25(13):7252. doi: 10.3390/ijms25137252.
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.
免疫检查点抑制剂 (ICIs) 与化疗相比，在癌症患者中显示出持久的反应、长期生存获益和改善的结果。然而，大多数癌症患者对 ICI 没有反应，并且很大比例对 ICI 治疗有反应的患者对 ICI 产生先天或获得性耐药，限制了其临床应用。最受研究的预测 ICI 反应的组织生物标志物是 PD-L1 免疫组化表达、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。确定更好的预测生物标志物仍然是一个重要目标，以提高识别从 ICI 中受益的患者的能力。在这里，我们回顾了 ICI 反应的既定和新兴生物标志物，重点关注癌症患者的表观基因组和基因组改变，这些改变有可能帮助指导单药 ICI 免疫治疗或 ICI 免疫治疗联合其他 ICI 免疫疗法或药物。我们简要回顾了 ICI 反应生物标志物的当前状况，包括研究中的生物标志物，并介绍了几个新兴和有前途的表观基因组生物标志物候选物的见解，包括在黑色素瘤患者的 ICI 免疫治疗反应背景下的当前知识空白。
