Review Article

Metformin and cancer immunity

Authors: Ruixia Ma1,2,3, Bin Yi1,2, Adam I. Riker4, Yaguang Xi1,2
1 Department of Genetics, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA
2 Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA
3 Present address: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou 221000, China
4 Geaton and JoAnn DeCesaris Cancer Institute, Anne Arundel Medical Center, Luminis Health, Annapolis, MD, USA
Correspondence to: Adam I. Riker: ariker@aahs.org, Yaguang Xi: yxi@lsuhsc.edu,
DOI: 10.1038/s41401-020-00508-0
Received: 27 May 2020
Accepted: 13 August 2020
Advance online: 31 August 2020

Abstract

The immune system plays an essential and central role in tumor cell differentiation, proliferation, angiogenesis, apoptosis, invasion, and metastasis. Over the past decade, cancer therapy has rapidly evolved from traditional approaches, such as surgery, chemotherapy, and radiotherapy, to revolutionary new treatment options with immunotherapy. This new era of cancer treatment options has now been clinically tested and applied to many forms of human malignancies, often with quite dramatic results. As we develop more effective combinations of cancer treatment, several agents have been recently investigated, putatively identified as anticancer agents, or immunostimulatory molecules. One such agent is metformin, originally developed as a fairly standard first-line therapy for patients with type-2 diabetes mellitus (T2DM). Given the underlying mechanisms of action, researchers began to examine the alternative functions and possible utility of metformin, finding that the cancer risk in patients with T2DM was reduced. It appears that metformin, at least in part, has an antitumor effect through activation of the 5’ adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Moreover, numerous studies have demonstrated that metformin interferes with key immunopathological mechanisms that are involved in the pathological processes or associated with malignant progression. Such insights may shed light on further analyzing whether metformin enhances the effectiveness of the immunotherapy and overcomes the immunotherapy resistance in the patients. Herein, we provide a comprehensive review of the literature examining the impact of metformin upon the host immune system and cancer immunity.
Keywords: metformin; cancer; immunity; immunotherapy

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