Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner.
Oncoimmunology
; 10(1): 1995999, 2021.
Article
em En
| MEDLINE
| ID: mdl-34745769
ABSTRACT
Metformin, a drug prescribed to treat type 2 diabetes, has been reported to possess antitumor activity via immunity activation. However, the influence of metformin on natural killer (NK) cells is not fully understood. Here, we investigated whether metformin exerts a potent anticancer effect by activating NK cells. The results showed that sustained exposure to metformin enhances the cytolytic activity of NK-92 cells. Moreover, this enhancement of cytotoxicity by metformin was also observed in NK cells from healthy peripheral blood and cancer patient ascites. Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner. In vivo experiments, metformin also improved cancer surveillance of NK cells in mouse models of lymphoma clearance and metastatic melanoma. Additionally, combination treatment with metformin and anti-PD-1 antibodies increased the therapy response rates of B16F10 melanoma. Moreover, metformin treatment increased NK cell and T cell infiltration in tumors. Therefore, these results provide a deeper understanding of metformin on the effector function of NK cells and will contribute to the development and applications of metformin in cancer treatment strategies.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Melanoma
/
Metformina
Limite:
Animals
Idioma:
En
Revista:
Oncoimmunology
Ano de publicação:
2021
Tipo de documento:
Article