Anti-PD-1 checkpoint blockade improves the efficacy of a melphalan-based therapy in experimental melanoma.
Eur J Surg Oncol
; 47(9): 2460-2464, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-33980416
ABSTRACT
INTRODUCTION:
The induction of adaptive cellular immunity in patients with in-transit melanoma metastasis treated with hyperthermic isolated limb perfusion (ILP) with melphalan has been shown to contribute to the effectiveness of the therapy. Activated CD8+ T cells appear to be of particular importance for the efficacy of melphalan-based ILP therapy, as observed in both patients and animal models. In this study, we explored the possible synergistic effects of combining melphalan-based therapy with the checkpoint inhibitor anti-PD-1 on tumours in a mouse melanoma model.METHODS:
A murine vaccination model that utilized melphalan-exposed melanoma cells was used to mimic certain immunological features of melphalan-based ILP. The effects of the vaccine on tumour growth and PD-1 expression on CD8+ tumour-infiltrating T cells were analyzed. The melphalan-based vaccine was then combined with an anti-PD-1 antibody and tumour growth was assessed.RESULTS:
Treatment with melphalan-based therapy significantly induced the expression of PD-1 on CD8+ tumour-infiltrating lymphocytes. Combination therapy using melphalan-based therapy followed by treatment with PD-1 antibodies significantly reduced early-stage tumour growth relative to monotherapies and no treatment.CONCLUSIONS:
This study thus suggests that the addition of PD-1 blockade to melphalan-based therapies, such as ILP, may be therapeutically beneficial.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Melanoma Experimental
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Receptor de Morte Celular Programada 1
/
Imunoterapia
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article