免疫检查点抑制剂（ICI）联合疗法在晚期胆道癌（BTC）的一线治疗中显示出前景。然而，最佳合作伙伴仍有待验证。此外，预测 ICI 对 BTC 疗效的生物标志物进展缓慢。本研究旨在评估程序性细胞死亡蛋白-1（PD-1）抗体联合疗法在晚期 BTC 一线治疗中的疗效并研究可靠的预测生物标志物。来自接受化疗或抗肿瘤药物治疗的晚期 BTC 患者的临床数据。收集了作为一线的PD-1联合疗法。主要结局是总生存期（OS）。研究了生物标志物，包括外周血炎症评分、基因改变和肿瘤微环境。招募了 64 名患者，分为四个治疗组：化疗组、抗 PD-1 加化疗、抗 PD-1 加靶向治疗组和抗 PD-1 加靶向治疗组。三联组（抗PD-1加化疗和靶向治疗）。中位 OS 分别为 7.9、11.3、12.8 和 28.7 个月。与化疗相比，三联组的 mOS 显着延长 (p = 0.031)。结果显示，具有五种不同外周血炎症评分的患者的 mOS 显着延长（p<<0.05）。基因检测结果表明，生存率较差的患者均存在TP53突变以及较高水平的KRAS和ERBB2突变。低 FOXP3/CD8 比率与延长 OS 相关 (p = 0.029)。以TME中CD4-low、CD8-high、CD56-positive、CD163-high、FOXP3-high和MPO-high作为1个因素，根据因素个数计算PLUS评分。高PLUS（>2）组表现出显着优越的OS（p = 0.003）。一线抗PD-1联合治疗优于化疗，三联疗法显着提高生存率。外周血免疫炎症评分、FOXP3/CD8 比值和 PLUS 有潜力作为生物标志物，用于预测一线抗 PD-1 疗法在晚期 BTC 中的疗效。© 2023 作者。约翰·威利出版的癌症医学

Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first-line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein-1 (PD-1) antibody combination therapy in the first-line treatment of advanced BTC.Clinical data from patients with advanced BTC who received chemotherapy or anti-PD-1 combination therapy as first-line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated.Sixty-four patients were recruited and divided into four treatment groups: chemotherapy, anti-PD-1 plus chemotherapy, anti-PD-1 plus targeted therapy, and triple group (anti-PD-1 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7 months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (p = 0.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (p < 0.05). Genetic testing results suggested that patients with poor survival all had TP53 mutations and higher levels of KRAS and ERBB2 mutations. Low FOXP3/CD8 ratio was associated with prolonged OS (p = 0.029). With CD4-low, CD8-high, CD56-positive, CD163-high, FOXP3-high and MPO-high in TME as one factor, we calculated PLUS score according to the number of factors. The high-PLUS (>2) group showed significantly superior OS (p = 0.003).First-line anti-PD-1 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune-inflammation score, FOXP3/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first-line anti-PD-1 therapy in advanced BTC.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.