Possible mechanism for improving the endogenous immune system through the blockade of peripheral µ-opioid receptors by treatment with naldemedine.
Br J Cancer
; 127(8): 1565-1574, 2022 11.
Article
en En
| MEDLINE
| ID: mdl-35945243
ABSTRACT
BACKGROUND:
It has been considered that activation of peripheral µ-opioid receptors (MORs) induces side effects of opioids. In this study, we investigated the possible improvement of the immune system in tumour-bearing mice by systemic administration of the peripheral MOR antagonist naldemedine.METHODS:
The inhibitory effect of naldemedine on MOR-mediated signalling was tested by cAMP inhibition and ß-arrestin recruitment assays using cultured cells. We assessed possible changes in tumour progression and the number of splenic lymphocytes in tumour-bearing mice under the repeated oral administration of naldemedine.RESULTS:
Treatment with naldemedine produced a dose-dependent inhibition of both the decrease in the cAMP level and the increase in ß-arrestin recruitment induced by the MOR agonists. Repeated treatment with naldemedine at a dose that reversed the morphine-induced inhibition of gastrointestinal transport, but not antinociception, significantly decreased tumour volume and prolonged survival in tumour-transplanted mice. Naldemedine administration significantly decreased the increased expression of immune checkpoint-related genes and recovered the decreased level of toll-like receptor 4 in splenic lymphocytes in tumour-bearing mice.CONCLUSIONS:
The blockade of peripheral MOR may induce an anti-tumour effect through the recovery of T-cell exhaustion and promotion of the tumour-killing system.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Opioides mu
/
Neoplasias
Límite:
Animals
Idioma:
En
Revista:
Br J Cancer
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón