Signal Transducer and Activation of Transcription 3: A Master Regulator of Myeloid-Derived Suppressor Cells

Abstract

Cancer progression is determined by cancer cells as well as various immune cells that make up the tumor microenvironment (TME). These immune cells consist of so-called effector cells such as natural killer cells and cytotoxic T lymphocytes, which fight cancer progression, and of immunosuppressive immune cells including regulatory T cells and immature myeloid cells, which aid tumor progression. Immature myeloid cells in the TME are further divided into several populations, amongst which are tumor-associated dendritic cells (TADC), tumor-associated macrophages (TAM), and myeloid-derived suppressor cells (MDSC). While TADC and TAM can be found in different activation states, MDSC can be further subdivided in two subsets: polymorphonuclear and monocytic MDSC. In recent years, MDSC received much attention as they are believed to exert a plethora of inhibitory mechanisms to create a tumor promoting TME. The recruitment, activation, and function of MDSC in the TME are largely determined by the transcription factor signal transducer and activator of transcription 3 (STAT3). Therefore, this review will focus on the role of this key signaling pathway during the MDSC life cycle.