Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer

Ludovic Fournel, Zherui Wu, Nicolas Stadler, Diane Damotte, Filippo Lococo, Geoffroy Boulle, Evelyne Ségal-Bendirdjian, Antonio Bobbio, Philippe Icard, Jean Trédaniel, Marco Alifano, Patricia Forgez

Research output: Contribution to journalArticle

Abstract

The number of clinical protocols testing combined therapies including immune check-point inhibitors and platinum salts is currently increasing in lung cancer treatment, however preclinical studies and rationale are often lacking. Here, we evaluated the impact of cisplatin treatment on PD-L1 expression analyzing the clinicopathological characteristics of patients who received cisplatin-based neoadjuvant chemotherapy followed by surgery and showed that cisplatin-based induction treatment significantly increased PD-L1 staining in both tumor and immune cells from the microenvironment. Twenty-two patients exhibited positive PD-L1 staining variation after neoadjuvant chemotherapy; including 9 (23.1%) patients switching from <50% to ≥50% of stained tumor-cells. We also confirmed the up-regulation of PD-L1 by cisplatin, at both RNA and protein levels, in nude and immunocompetent mice bearing tumors grafted with A549, LNM-R, or LLC1 lung cancer cell lines. The combined administration of anti-PD-L1 antibodies (3 mg/kg) and cisplatin (1 mg/kg) to mice harboring lung carcinoma significantly reduced tumor growth compared to single agent treatments and controls. Overall, these results suggest that cisplatin treatment could synergize with PD-1/PD-L1 blockade to increase the clinical response, in particular through early and sustainable enhancement of PD-L1 expression.

Original languageEnglish
Pages (from-to)5-14
Number of pages10
JournalCancer Letters
Volume464
DOIs
Publication statusPublished - Nov 1 2019

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Keywords

  • Cisplatin
  • Immune check-point inhibitors
  • Lung cancer
  • Neoadjuvant treatment
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fournel, L., Wu, Z., Stadler, N., Damotte, D., Lococo, F., Boulle, G., Ségal-Bendirdjian, E., Bobbio, A., Icard, P., Trédaniel, J., Alifano, M., & Forgez, P. (2019). Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer. Cancer Letters, 464, 5-14. https://doi.org/10.1016/j.canlet.2019.08.005