Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer.
Cancer Lett
; 464: 5-14, 2019 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-31404614
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 (3â¯mg/kg) and cisplatin (1â¯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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cisplatin
/
Carcinoma, Non-Small-Cell Lung
/
B7-H1 Antigen
/
Antineoplastic Agents, Immunological
/
Lung Neoplasms
Type of study:
Guideline
/
Prognostic_studies
Limits:
Aged
/
Animals
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Cancer Lett
Year:
2019
Document type:
Article