PLoS ONE (Jan 2021)

Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers.

  • 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,
  • Shunichi Sugawara

DOI
https://doi.org/10.1371/journal.pone.0260500
Journal volume & issue
Vol. 16, no. 11
p. e0260500

Abstract

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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.