Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner

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 activ...

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Autores principales:	Wenjiao Xia, Xin Qi, Mingfeng Li, Yu Wu, Lulu Sun, Xinglong Fan, Yuan Yuan, Jing Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	metformin nk cells cancer surveillance immunotherapy p38 mapk Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ffd0b0086e204654bfbb2c1ff0c79ebd
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spelling	oai:doaj.org-article:ffd0b0086e204654bfbb2c1ff0c79ebd2021-11-04T15:00:45ZMetformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner2162-402X10.1080/2162402X.2021.1995999https://doaj.org/article/ffd0b0086e204654bfbb2c1ff0c79ebd2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.1995999https://doaj.org/toc/2162-402XMetformin, 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.Wenjiao XiaXin QiMingfeng LiYu WuLulu SunXinglong FanYuan YuanJing LiTaylor & Francis Grouparticlemetforminnk cellscancer surveillanceimmunotherapyp38 mapkImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	metformin nk cells cancer surveillance immunotherapy p38 mapk Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	metformin nk cells cancer surveillance immunotherapy p38 mapk Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wenjiao Xia Xin Qi Mingfeng Li Yu Wu Lulu Sun Xinglong Fan Yuan Yuan Jing Li Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner
description	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.
format	article
author	Wenjiao Xia Xin Qi Mingfeng Li Yu Wu Lulu Sun Xinglong Fan Yuan Yuan Jing Li
author_facet	Wenjiao Xia Xin Qi Mingfeng Li Yu Wu Lulu Sun Xinglong Fan Yuan Yuan Jing Li
author_sort	Wenjiao Xia
title	Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner
title_short	Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner
title_full	Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner
title_fullStr	Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner
title_full_unstemmed	Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner
title_sort	metformin promotes anticancer activity of nk cells in a p38 mapk dependent manner
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/ffd0b0086e204654bfbb2c1ff0c79ebd
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_version_	1718444815238037504

Metformin promotes anticancer activity of NK cells in a p38 MAPK dependent manner

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