Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39CD73 MDSC and a concomitant increase in the antitumor activities of circulating CD8 T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients. The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. .

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882589PMC
http://dx.doi.org/10.1158/0008-5472.CAN-17-2460DOI Listing

Publication Analysis

Top Keywords

ovarian cancer
16
patients ovarian
12
metformin-induced reduction
8
cd39 cd73
8
myeloid-derived suppressor
8
antitumor activity
8
metformin treatment
8
suppressor cells
8
mdsc metformin
8
activity
6

Similar Publications

Background: Several approaches are being explored for engineering off-the-shelf chimeric antigen receptor (CAR) T cells. In this study, we engineered chimeric Fcγ receptor (FcγR) T cells and tested their potential as a versatile platform for universal T cell therapy.

Methods: Chimeric FcγR (CFR) constructs were generated using three distinct forms of FcγR, namely CD16A, CD32A, and CD64.

View Article and Find Full Text PDF

Background: Whether the intake of whole grain foods can protect against lung cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been limited. Therefore we aim to investigate the relationship between whole grain food consumption and lung cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.

Methods: Diet was assessed with a self-administered Diet History Questionnaire (DHQ) at baseline.

View Article and Find Full Text PDF

Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Oxidative stress-induced growth inhibitor 1 (OSGIN1), which is a tumor suppressor gene known to regulate the cellular stress response and apoptosis, is associated with ovarian cancer development. However, the underlying mechanisms involved in ferroptosis regulation have not been elucidated.

View Article and Find Full Text PDF

Familial History in Ovarian Teratomas Is a Frequent Event: 22 Years' Experience at a Single Center.

Pediatr Blood Cancer

January 2025

Department of Pediatric Surgery, Urology and Transplantation, Hôpital Universitaire Necker-Enfants Malades, APHP, Université de Paris Cité, Paris, France.

Background: Ovarian mature teratoma represents the most common benign neoplasm among pediatric germ cell tumors. This study reports the prevalence and characteristics of familial forms identified in a single center over 22 years in order to better understand possible familial predispositions to ovarian teratoma.

Methods: The records of all patients who were surgically treated for ovarian teratoma between 2000 and 2022 were retrospectively reviewed.

View Article and Find Full Text PDF

Objectives: Sedentary behaviour (SB) is associated with increased risks of breast, colorectal, endometrial, ovarian and rectal cancers. However, the number of cancer cases attributable to SB in Germany and the associated costs are unknown.

Setting: Numbers and proportions (population-attributable fractions, PAF) of new cancer cases attributable to SB with published risk estimates for Germany for the years 2024, 2030 and 2040.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!