Chen Hui-Zi, Kim Na Hyun, Nishizaki Daisuke, Nesline Mary K, Conroy Jeffrey M, DePietro Paul, Pabla Sarabjot, Kato Shumei, Kurzrock Razelle
Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA.
Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
NPJ Genom Med. 2025 Mar 11;10(1):21. doi: 10.1038/s41525-025-00465-9.
Programmed cell death protein 1 (PD-1) is a critical immune checkpoint receptor and a target for cancer immune checkpoint inhibitors (ICI). We investigated PD-1 transcript expression across cancer types and its correlations to clinical outcomes. Using a reference population, PD-1 expression was calculated as percentiles in 489 of 514 patients (31 cancer types) with advanced/metastatic disease. PD-1 RNA expression varied across and within cancer types; pancreatic and liver/bile duct malignancies displayed the highest rates of high PD-1 (21.82% and 21.05%, respectively). Elevated CTLA-4, LAG-3, and TIGIT RNA expression were independently correlated with high PD-1. Although high PD-1 was not associated with outcome in immunotherapy-naïve patients (n = 272), in patients who received ICIs (n = 217), high PD-1 transcript expression was independently correlated with prolonged survival (hazard ratio 0.40; 95%CI, 0.18-0.92). This study identifies PD-1 as an important biomarker in predicting ICI outcomes, and advocates for comprehensive immunogenomic profiling in cancer management.
程序性细胞死亡蛋白1（PD-1）是一种关键的免疫检查点受体，也是癌症免疫检查点抑制剂（ICI）的靶点。我们研究了PD-1转录本在不同癌症类型中的表达及其与临床结局的相关性。利用一个参考人群，在514例患有晚期/转移性疾病的患者（31种癌症类型）中的489例中，将PD-1表达计算为百分位数。PD-1 RNA表达在不同癌症类型之间以及同一癌症类型内部均有所不同；胰腺癌和肝/胆管恶性肿瘤中高PD-1的发生率最高（分别为21.82%和21.05%）。CTLA-4、LAG-3和TIGIT RNA表达升高与高PD-1独立相关。虽然在未接受过免疫治疗的患者（n = 272）中，高PD-1与结局无关，但在接受ICI治疗的患者（n = 217）中，高PD-1转录本表达与生存期延长独立相关（风险比0.40；95%CI，0.18 - 0.92）。本研究将PD-1确定为预测ICI治疗结局的重要生物标志物，并提倡在癌症管理中进行全面的免疫基因组分析。
