Immune Suppressive Myeloid-Derived Suppressor Cells in Cancer

Abstract

Myeloid-derived suppressor cells (MDSC) accumulate in individuals with a variety of conditions. These conditions typically involve inflammation and range from an inflammatory tumor microenvironment to infection and stress. MDSCs also accumulate with aging. The cells are present at low levels in healthy and young individuals; however, when elevated, MDSC are profoundly immune suppressive cells that neutralize natural immunity and impede strategies for activating the immune system to cancer or infectious diseases. A variety of proinflammatory mediators acting through multiple receptors drive the accumulation of MDSC from myeloid progenitor cells. In the tumor microenvironment, MDSC facilitate tumor progression not only through the multiple mechanisms they use to inhibit both the innate and adaptive immune systems, but also through their nonimmune effects that promote angiogenesis and tumor invasion and metastasis. Various therapeutic strategies have been tested to neutralize or eliminate MDSC. However, none of these therapies are universally effective due to the heterogeneity and diversity of MDSC. The goal of eliminating or neutralizing MDSC in cancer patients is currently being pursued both experimentally and in clinical trials.