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

2019; Elsevier BV; Volume: 464; Linguagem: Inglês

10.1016/j.canlet.2019.08.005

1872-7980

Ludovic Fournel, Zherui Wu, Nicolas Städler, Diane Damotte, Filippo Lococo, G. Boulle, E. Segal, Antonio Bobbio, Philippe Icard, Jean Trédaniel, Marco Alifano, Patricia Forgez,

Immunotherapy and Immune Responses

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.