Myeloid Derived Suppressor Cells (MDSCs): the Key to Understanding Chronic Inflammation and its Complications in Cancer

Chronic inflammation is typical to various chronic diseases and is associated with immunosuppression. In such conditions, a variety of inflammatory factors induce the accumulation of highly suppressive myeloid-derived suppressor cells (MDSCs), thus manipulating the host’s immune function and suppressing the innate and adaptive arms of the immune system. The immunosuppression is reflected by down-regulation of CD247 expression in T and NK cells, resulting in their dysfunction. Such chronic inflammation-induced immunosuppressive conditions are also found in many caces of cancer, generating a suppressive - MDSC enriched tumor micro- and macro-environments. MDSCs act as critical barriers inpreventing beneficial anti-tumor responses and severely reducing the efficacy of anti cancer therapies. Our research focuses on the mechanisms underlying the biology of MDSCs such as chemokine receptors, epigenetics and exosome production in the various MDSC-related complications. We demonstrate that the environment generated under non-cancerous and cancerous chronic inflammatory settings is harmful to the host, leading to a broad spectrum ofcomplications:1) Impared immune responses and increased susceptibility to oportunistic ifections. 2) Deleterious changes in the cross-talk between gut inflammation and micro-biota, predisposing the host to colorectal cancer development. 3) Injurious changes in bone homeostasis leading to bone lose.

Understanding the function of MDSCs at the molecular levels and the physiological and immunological consequences could offer new and novel candidate immune targets for therapeutic interventions. Combination of such treatments with chemotherapy and other conventional approaches in cancer targeted therapy, may prevent chronic inflammation and MDSC associated complications and increase treatment`s efficacy. A better identification of environmental and tumor-specific inflammatory mechanisms will allow directing the clinical management of cancer toward a more personalized medicine.