PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome. NPJ Genom Med 2025 Mar 11;10(1):21
Date
03/12/2025Pubmed ID
40069238Pubmed Central ID
PMC11897377DOI
10.1038/s41525-025-00465-9Scopus ID
2-s2.0-105000032476 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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.
Author List
Chen HZ, Kim NH, Nishizaki D, Nesline MK, Conroy JM, DePietro P, Pabla S, Kato S, Kurzrock RAuthors
Hui-Zi Chen PhD, MD Assistant Professor in the Medicine department at Medical College of WisconsinRazelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
