Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Department of Biliary Tract Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
J Leukoc Biol. 2021 Aug;110(2):327-334. doi: 10.1002/JLB.5MA1220-631R. Epub 2021 Mar 16.
Predictive prognostic markers for immunotherapy are crucial and desperately required for clinical precise medicine. This retrospective study aimed to assess the efficacy of anti-PD-1 (programmed cell death protein 1) treatment and find the therapeutic prognostic biomarkers in advanced biliary tract cancer (BTC). A total of 60 patients of advanced BTC who received at least one dose of anti-PD-1 therapy between June 2016 and October 2019 were recruited and followed up till April 2020. Systemic immune-inflammation index (SII) and neutrophils-to-lymphocytes ration (NLR) were obtained from the routine circulating hematologic analysis before treatment. Serum 45-Plex Panel cytokines were detected using multiplexed bead immunoassays. Logistic regression nomogram was used to construct the algorithm model for prognosis prediction. Of the 60 patients, the overall benefit rate (OBR) was 38.3%, the median progression free survival (PFS), and overall survival (OS) were 4.0 mo (95% confidence interval [CI]: 2.28-5.72) and 13.0 mo (95% CI: 8.05-17.95), respectively. High levels of SII (≥720), NLR (≥4.3) and cytokine IFN-inducible protein-10 (IP-10; ≥45 pg/ml) indicated worse OS. Those with high SII (≥720) and high IP-10 (≥45 pg/ml) also had shorter PFS. The nomogram algorithm combining above three independent factors (SII, IP-10, and macrophage inflammatory protein-1β) had better efficacy in predicting OBR. Our study offers a simple, affordable, and noninvasive method to help physicians predict therapeutic response in BTC patients receiving anti-PD-1 antibody treatment.
预测性预后标志物对于免疫疗法至关重要,是临床精准医学所急需的。本回顾性研究旨在评估抗 PD-1(程序性细胞死亡蛋白 1)治疗的疗效,并寻找晚期胆道癌(BTC)的治疗预后生物标志物。共招募了 60 名接受至少一剂抗 PD-1 治疗的晚期 BTC 患者,这些患者于 2016 年 6 月至 2019 年 10 月接受治疗,并随访至 2020 年 4 月。在治疗前,从常规循环血液学分析中获得了系统免疫炎症指数(SII)和中性粒细胞与淋巴细胞比值(NLR)。使用多指标珠免疫分析检测血清 45-Plex 面板细胞因子。使用逻辑回归列线图构建预后预测算法模型。在 60 名患者中,总体缓解率(OBR)为 38.3%,中位无进展生存期(PFS)和总生存期(OS)分别为 4.0 个月(95%置信区间 [CI]:2.28-5.72)和 13.0 个月(95% CI:8.05-17.95)。SII(≥720)、NLR(≥4.3)和细胞因子干扰素诱导蛋白-10(IP-10;≥45pg/ml)水平较高提示 OS 较差。SII(≥720)和 IP-10(≥45pg/ml)较高的患者 PFS 也较短。结合上述三个独立因素(SII、IP-10 和巨噬细胞炎症蛋白-1β)的列线图算法在预测 OBR 方面具有更好的效果。我们的研究提供了一种简单、经济、非侵入性的方法,有助于医生预测接受抗 PD-1 抗体治疗的 BTC 患者的治疗反应。