Myeloid Derived Suppressor Cells as Plastic Sensors and Outcome Orchestrators During Chronic Inflammation

In pathologies characterized by chronic inflammation altered myelopoiesis is evident, which is associated with the accumulation of myeloid derived suppressor cells (MDSCs). MDSCs are characterized by diverse phenotypes and functions, they are arrested in their immature state, are polarized towards highly suppressive cells and migrate from the bone marrow to the periphery and sites of inflammation, where they impair effector functions of innate and adaptive immune cells, promote tumor growth, angiogenesis, and tissue damage. When reaching new environments, which exhibit a different array of cytokines, chemokines, and pro-inflammatory mediators, MDSCs sense and adapt to the altered micro-environment by virtue of acquiring different features that involve changing their cell fate, surface receptors, metabolism and intracellular as well as secreted molecules. Based on the plasticity and biological diversity of MDSCs, they have a dual use: 1) As biomarkers for the evaluation of chronic inflammation-induced complications and for the prediction of success rates of immune based therapies, and 2) As targets for treatments aimed at combating them or manipulating their differentiation state or suppressive activity towards achieving recuperated homeostasis and/or improving therapies in various pathologies characterized by chronic inflammation. Examples for MDSCs as plastic sensors and outcome orchestrators will be presented and the clinical implications will be highlighted.