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Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers
- Source :
- PLoS ONE, PLoS ONE, Vol 16, Iss 11, p e0260500 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- Although anti-PD-1/PD-L1 monotherapy has achieved clinical success in non-small cell lung cancer (NSCLC), definitive predictive biomarkers remain to be elucidated. In this study, we performed whole-transcriptome sequencing of pretreatment tumor tissue samples and pretreatment and on-treatment whole blood samples (WB) samples obtained from a clinically annotated cohort of NSCLC patients (n = 40) treated with nivolumab (anti-PD-1) monotherapy. Using a single-sample gene set enrichment scoring method, we found that the tumors of responders with lung adenocarcinoma (LUAD, n = 20) are inherently immunogenic to promote antitumor immunity, whereas those with lung squamous cell carcinoma (LUSC, n = 18) have a less immunosuppressive tumor microenvironment. These findings suggested that nivolumab may function as a molecular targeted agent in LUAD and as an immunomodulating agent in LUSC. In addition, our study explains why the reliability of PD-L1 expression on tumor cells as a predictive biomarker for the response to nivolumab monotherapy is quite different between LUAD and LUSC.
- Subjects :
- Male
Lung Neoplasms
Physiology
Gene Expression
Biochemistry
Lung and Intrathoracic Tumors
Cohort Studies
Carcinoma, Non-Small-Cell Lung
Gene expression
Medicine and Health Sciences
Immune Response
Immune Checkpoint Inhibitors
Energy-Producing Organelles
Whole blood
Aged, 80 and over
Multidisciplinary
Drugs
Middle Aged
Immunosuppressives
Body Fluids
Mitochondria
Gene Expression Regulation, Neoplastic
Blood
Nivolumab
medicine.anatomical_structure
Oncology
Medicine
Adenocarcinoma
Female
Anatomy
Cellular Structures and Organelles
Immunomodulating Agent
Research Article
Science
Immunology
Bioenergetics
Immune system
Genetics
medicine
Humans
Aged
Pharmacology
Tumor microenvironment
Lung
business.industry
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
medicine.disease
Non-Small Cell Lung Cancer
Cancer research
Transcriptome
business
Biomarkers
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....57499764501b85f7a6a57fadeae39bfe
- Full Text :
- https://doi.org/10.1371/journal.pone.0260500