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Dissecting transcriptome signals of anti-PD-1 response in lung adenocarcinoma.
- Source :
-
Scientific reports [Sci Rep] 2024 Sep 10; Vol. 14 (1), pp. 21096. Date of Electronic Publication: 2024 Sep 10. - Publication Year :
- 2024
-
Abstract
- Immune checkpoint blockades are actively adopted in diverse cancer types including metastatic melanoma and lung cancer. Despite of durable response in 20-30% of patients, we still lack molecular markers that could predict the patient responses reliably before treatment. Here we present a composite model for predicting anti-PD-1 response based on tumor mutation burden (TMB) and transcriptome sequencing data of 85 lung adenocarcinoma (LUAD) patients who received anti-PD-(L)1 treatment. We found that TMB was a good predictor (AUC = 0.81) for PD-L1 negative patients (n = 20). For PD-L1 positive patients (n = 65), we built an ensemble model of 100 XGBoost learning machines where gene expression, gene set activities and cell type composition were used as input features. The transcriptome-based models showed excellent accuracy (AUC > 0.9) and highlighted the contribution of T cell activities. Importantly, nonresponder patients with high prediction score turned out to have high CTLA4 expression, which suggested that neoadjuvant CTLA4 combination therapy might be effective for these patients. Our data and analysis results provide valuable insights into developing biomarkers and strategies for treating LUAD patients using immune checkpoint inhibitors.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Biomarkers, Tumor genetics
B7-H1 Antigen metabolism
B7-H1 Antigen genetics
Programmed Cell Death 1 Receptor metabolism
Programmed Cell Death 1 Receptor antagonists & inhibitors
Programmed Cell Death 1 Receptor genetics
Mutation
CTLA-4 Antigen genetics
CTLA-4 Antigen metabolism
Gene Expression Regulation, Neoplastic
Female
Male
Gene Expression Profiling methods
Adenocarcinoma of Lung genetics
Adenocarcinoma of Lung drug therapy
Adenocarcinoma of Lung pathology
Adenocarcinoma of Lung metabolism
Adenocarcinoma of Lung immunology
Lung Neoplasms genetics
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Lung Neoplasms metabolism
Transcriptome
Immune Checkpoint Inhibitors therapeutic use
Immune Checkpoint Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39256604
- Full Text :
- https://doi.org/10.1038/s41598-024-72108-5