1. Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers.
- Author
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Tomoiki Aiba, Chieko Hattori, Jun Sugisaka, Hisashi Shimizu, Hirotaka Ono, Yutaka Domeki, Ryohei Saito, Sachiko Kawana, Yosuke Kawashima, Keisuke Terayama, Yukihiro Toi, Atsushi Nakamura, Shinsuke Yamanda, Yuichiro Kimura, Yutaka Suzuki, Atsushi Niida, and Shunichi Sugawara
- Subjects
Medicine ,Science - 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.
- Published
- 2021
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