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<p>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.</p>

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PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月11日

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  • Hui-Zi Chen,
  • Na Hyun Kim,
  • Daisuke Nishizaki,
  • Mary K. Nesline,
  • Jeffrey M. Conroy,
  • Paul DePietro,
  • Sarabjot Pabla,
  • Shumei Kato,
  • Razelle Kurzrock

摘要

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.