Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis.
Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis.
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肿瘤原发灶和配对转移灶之间免疫治疗反应预测生物标志物的不一致：系统评价和荟萃分析
DOI：
10.1016/j.ebiom.2020.103137
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发表时间：
2021-01
期刊：
影响因子：
11.1
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Zou Y;Hu X;Zheng S;Yang A;Li X;Tang H;Kong Y;Xie X
几种生物标志物可以预测免疫疗法的疗效，这对于选择可能受益的患者至关重要。这些生物标志物在原发肿瘤和成对转移瘤之间的不一致状态已经越来越多地被揭示。我们旨在全面总结这种现象的发生率。检索数据库，以确定报告生物标志物原发性至转移性转化的研究，包括程序性死亡配体-1（PD-L1）、程序性细胞死亡蛋白-1（PD-1）、PD-L2、肿瘤浸润淋巴细胞（TIL）、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）。纳入了56项研究，2739例患者。PD-L1的汇总不一致率为22%。PD-L1由阳性转为阴性的比例为41%，而由阴性转为阳性的比例为16%。PD-1和PD-L2的不一致率分别为26%和22%。TIL水平的不一致率为39%，由高到低的变化（50%）多于由低到高的变化（16%）。在大多数研究中，未观察到两个部位之间的TMB存在显著差异。6%的患者发现MSI状态不一致，从MSI高到微卫星不稳定（MSS）的百分比为9%，从MSS到MSI高的百分比为0%。我们的研究表明，PD-L1，PD-1，PD-L2和TIL水平具有高频率的不一致性，而TMB和MSI状态不太可能在原发性肿瘤和配对转移瘤之间发生变化。因此，强烈建议评估原发性和转移性肿瘤的那些经常改变的生物标志物，以准确做出免疫检查点治疗的临床决策。国家自然科学基金项目（81872152）。
Several biomarkers predict the efficacy of immunotherapy, which is essential for selecting patients who would potentially benefit. Discordant status of these biomarkers between primary tumours and paired metastases has been increasingly revealed. We aimed to comprehensively summarize the incidence of this phenomenon. Databases were searched to identify studies reporting primary-to-metastatic conversion of biomarkers, including programmed death ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), PD-L2, tumour-infiltrating lymphocyte (TIL), tumour mutational burden (TMB), and microsatellite instability (MSI). 56 studies with 2739 patients were included. The pooled discordance rate of PD-L1 was 22%. The percentage of PD-L1 changed from positive to negative was 41%, whereas that from negative to positive was 16%. The discordance rate for PD-1 and PD-L2 was 26% and 22%, respectively. TIL level was found with a discordance rate of 39%, and changes from high to low (50%) occurred more than that from low to high (16%). No significant difference in TMB was observed between two sites in most studies. MSI status discordance was found in 6% patients, with a percentage of 9% from MSI-high to microsatellite instable (MSS) and 0% from MSS to MSI-high. Our study demonstrates that PD-L1, PD-1, PD-L2, and TIL level had high frequency of discordance, while TMB and MSI status were less likely to change between primary tumours and paired metastases. Therefore, evaluating those frequently altered biomarkers of both primary and metastatic tumours is strongly recommended for precise clinical decision of immune checkpoint treatment. The National Natural Science Foundation of China (81872152).