Research progress of predictive markers related to immune checkpoint inhibitor therapy for colorectal cancer
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摘要: 以免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）为代表的免疫疗法开辟了肿瘤治疗的新纪元。目前ICIs已经广泛应用于晚期转移性结直肠癌患者的治疗。预测性标志物是精确筛选可从ICIs治疗中受益的患者群体的重要工具。本文回顾并总结了目前ICIs治疗结直肠癌重要的预测性标志物及其研究现状，包括错配修复缺陷及微卫星不稳定性、肿瘤突变负荷、DNA聚合酶ε/DNA聚合酶δ1以及PD-L1表达等。通过了解这些标志物对于结直肠癌ICIs治疗的响应及患者预后的预测价值，有助于指导临床医生筛选潜在获益人群，提高治疗效率，实现精准化治疗。Abstract: The use of immune checkpoint inhibitors (ICIs) for immunotherapy has launched a new era of tumor treatment. At present, ICIs are widely used in the treatment of patients with advanced metastatic colorectal cancer. Predictive markers are important tools for accurately screening patients that can benefit from ICIs. This paper reviews and summarizes the uses of predictive markers in the treatment of colorectal cancer with ICIs. For example, the paper includes discussions of markers for mismatch repair defects and microsatellite instability, tumor mutation burden, DNA polymerase ε/DNA polymerase δ1, and PD-L1 expression. Understanding the predictive value of these markers for treatment response and patient prognosis will help doctors to screen potential beneficiaries, improve treatment efficiency and provide more accurate treatment.
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表 1 结直肠癌ICIs治疗相关预测性标志物
标志物名称 概述 dMMR/MSI-H 结直肠癌ICIs治疗的主要预测性分子标志物 TMB 具有较高的应用价值，需要确定合理的截断值来定义不同肿瘤突变负荷的患者 PD-L1表达 受限于PD-L1的检测，需要更多的研究确定检测结直肠癌PD-L1表达的统一标准 DNA聚合酶ε或聚合酶δ1突变 仍需更多试验证据支持POLE / POLD1突变作为结直肠癌ICIs治疗的分子标志物 免疫细胞相关标志物 包括免疫评分、中性粒细胞-淋巴细胞比率等，仍需进一步的临床实验探索其应用价值 
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