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PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome
Hui-Zi Chen1,2, Na Hyun Kim3, Daisuke Nishizaki4
1Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA. huchen@mcw.edu.
NPJ Genomic Medicine
|March 12, 2025
Summary
High programmed cell death protein 1 (PD-1) RNA expression predicts better survival in cancer patients treated with immune checkpoint inhibitors (ICI). This finding highlights PD-1 as a key biomarker for ICI therapy outcomes.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Programmed cell death protein 1 (PD-1) is a crucial immune checkpoint receptor targeted by cancer immune checkpoint inhibitors (ICI).
- Understanding PD-1 expression patterns and their clinical relevance is vital for optimizing cancer immunotherapy.
Purpose of the Study:
- To investigate PD-1 transcript expression across diverse cancer types.
- To correlate PD-1 expression with clinical outcomes, particularly in patients receiving ICI therapy.
Main Methods:
- PD-1 RNA expression was analyzed as percentiles in 489 patients with advanced/metastatic disease across 31 cancer types.
- Correlations between PD-1 expression and other immune checkpoint markers (CTLA-4, LAG-3, TIGIT) were assessed.
- The association between high PD-1 expression and patient outcomes was evaluated in both immunotherapy-naïve and ICI-treated cohorts.
Main Results:
- PD-1 RNA expression exhibited significant variability across and within cancer types, with pancreatic and liver/bile duct cancers showing the highest prevalence of high PD-1 expression.
- Elevated RNA expression of CTLA-4, LAG-3, and TIGIT were independently associated with high PD-1 expression.
- While high PD-1 expression did not correlate with outcomes in immunotherapy-naïve patients, it was independently linked to prolonged survival in patients treated with ICIs (HR 0.40; 95% CI, 0.18-0.92).
Conclusions:
- PD-1 transcript expression is a significant biomarker for predicting response and survival in patients undergoing cancer immune checkpoint inhibitor therapy.
- Comprehensive immunogenomic profiling, including PD-1 expression, should be integrated into cancer management strategies to personalize treatment and improve patient outcomes.
