POLE/POLD1突变在肿瘤免疫治疗预后中的价值

Prognostic Value of POLE/POLD1 Mutation in Cancer Immunotherapy

免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)已在多种肿瘤中显示出持续的临床疗效。错配修复蛋白缺陷(mismatch repair deficient,dMMR)或微卫星高度不稳定性(microsatellite instability-high,MSI-H)的转移性结直肠癌患者已从免疫治疗中获益。然而,部分PD-L1阴性和微卫星稳定(microsatellite stability,MSS)型结直肠癌患者对免疫治疗也有持续的反应。因此,为了给患者制定最佳治疗方案,选择能够识别免疫检查点阻断疗效的可靠生物标志物,实现精准治疗是至关重要的。DNA聚合酶亚基的关键编码基因POLE/POLD1是除MSI-H和肿瘤突变负荷(tumor mutation burden,TMB)外,最具潜力的免疫治疗预测指标。全文就POLE/POLD1的分子机制及其突变在免疫治疗中的研究进展进行综述。

Immunotherapy such as immune checkpoint inhibitors(ICIs)therapy have shown sustained clinical efficacy in a variety of tumor types.Patients with microsatellite instability-high/mismatch repair deficient(MSI-H/dMMR)may benefit from immunotherapy.However,some patients with negative PD-L1 or microsatellite stability(MSS)also have a sustained response to immunotherapy.Therefore,in order to achieve precision treatment for patients,it is critical to select reliable biomarkers for predicting the efficacy of immune checkpoint blocking.The key encoding gene of DNA polymerase subunit—POLE/POLD1 is one of the most promising predictors of immunotherapy,besides of MSI-H and tumor mutation burden.In this article,the molecular mechanism of POLE/POLD1 and its recent advances in immunotherapy are reviewed.