Editorial: Two MDSC faces in obesity: Correcting metabolic dysfunctions but promoting tumor development

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells with broadly distinct phenotypical characteristics that fail to terminally differentiate into granulocytes, macrophages, or dendritic cells (DC) and exhibit a remarkable capacity to inhibit functions of T and NK cells by multiple mechanisms.1,2 MDSC derive from the bone marrow hematopoietic precursors due to the altering of myelopoiesis under chronic inflammatory conditions that are also typical for the tumor microenvironment and characterized by a long-term secretion and accumulation of inflammatory factors including IL-1β, IL-6, TNF-α, IFN-γ, vascular endothelial growth factor, GM-CSF, CCL2, CCL3, CCL4, CCL5, etc.2–4 The enrichment and activation of MDSC in the tumor microenvironment can induce a profound immunosuppression, leading to the tumor progression.1–4 Obesity can be defined as a main component of metabolic disorders that include also insulin resistance, fatty liver disease, hyperglycemia, dyslipidemia, and hypertension induced by caloric excess, sedentary lifestyle, and a genetic predisposition.5 These disorders are considered as a critical step, leading to the development of type 2 diabetes, atherosclerosis, and cancer. Chronic, low-grade inflammation is described to be a key feature of metabolic dysfunction. Indeed, adipose tissue of obese human and mice has been reported to be not only an inert energy-storing depot but also to secrete critical inflammatory mediators such as IL-1β, IL-6, TNF-α, etc. On the other side, chronic inflammation has been demonstrated to play an important role in cancer initiation and progression6 that emphasizes the link between obesity and cancer.7 Although many types of innate immune cells were found in adipose tissue and described to be implicated maintaining adipose homeostasis or in inflammation-mediated metabolic disorders, most publications on low-grade inflammation during obesity were focused on macrophage infiltration and function in adipose tissue.5 Recently, a role of other immune cell types (including, neutrophils, mast cells, NK cells, and DC) has been emerged as an important topic.5 However, the involvement of MDSC in the regulation of metabolic alterations during obesity remains poorly understood.