Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Letters Année : 2019

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

Résumé

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.
Fichier principal
Vignette du fichier
Cancer letters june2919.pdf (19.45 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03014320 , version 1 (19-11-2020)

Identifiants

  • HAL Id : hal-03014320 , version 1

Citer

Ludovic Fournel, Zherui Wu, Nicolas Stadler, Diane Damotte, Filippo Lococo, et al.. Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer. Cancer Letters, 2019, 464, pp.5-14. ⟨hal-03014320⟩
49 Consultations
222 Téléchargements

Partager

Gmail Facebook X LinkedIn More