Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors.
Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors.
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DOI：
10.1038/s41467-021-20935-9
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发表时间：
2021-02-01
影响因子：
16.6
通讯作者：
Morris LGT
中科院分区：
文献类型：
--
作者：
Valero C;Lee M;Hoen D;Weiss K;Kelly DW;Adusumilli PS;Paik PK;Plitas G;Ladanyi M;Postow MA;Ariyan CE;Shoushtari AN;Balachandran VP;Hakimi AA;Crago AM;Long Roche KC;Smith JJ;Ganly I;Wong RJ;Patel SG;Shah JP;Lee NY;Riaz N;Wang J;Zehir A;Berger MF;Chan TA;Seshan VE;Morris LGT
免疫检查点抑制剂（ICI）治疗已证明对多种癌症类型具有临床益处。由于只有一部分患者经历了临床获益，因此非常需要在不同实践环境中易于获得的生物标志物。在这里，在1714例接受ICI治疗的16种不同癌症类型患者的回顾性队列研究中，我们发现，在多种癌症类型的ICI治疗后，较高的嗜中性粒细胞与淋巴细胞比率（NLR）与总体和无进展生存率较差以及反应率和临床获益率较低显著相关。结合NLR和肿瘤突变负荷（TMB），NLR低/TMB高组中ICI获益的概率显著高于NLR高/TMB低组（OR = 3.22; 95% CI，2.26-4.58; P < 0.001）。NLR是一种具有成本效益和广泛可获得的生物标志物的合适候选者，并且可以与TMB组合以获得额外的预测能力。对于简单、可获得的生物标志物存在未满足的临床需求，以选择更有可能对免疫检查点疗法有反应的患者。在这里，作者表明，在接受免疫检查点抑制剂治疗的多癌症患者队列中，较低的嗜中性粒细胞与淋巴细胞比率与更好的总体和无进展生存期以及更高的应答率相关。
Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P < 0.001) in the NLR low/TMB high group compared to the NLR high/TMB low group. NLR is a suitable candidate for a cost-effective and widely accessible biomarker, and can be combined with TMB for additional predictive capacity. There is an unmet clinical need for simple, accessible biomarkers to select patients who are more likely to respond to immune checkpoint therapy. Here the authors show that a lower neutrophil-to-lymphocyte ratio is associated with better overall and progressive-free survival, as well as higher rate of response, in a multi-cancer cohort of patients treated with immune checkpoint inhibitors.
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