High‐mobility group box protein 1 promotes the survival of myeloid‐derived suppressor cells by inducing autophagy
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Type of Work8 pages
Citation of Original PublicationKatherine H. Parker, Lucas A. Horn, Suzanne Ostrand‐Rosenberg, High‐mobility group box protein 1 promotes the survival of myeloid‐derived suppressor cells by inducing autophagy, Journal of Leukocyte Biology, Spotlight on Leading Edge Research , 2016, https://doi.org/10.1189/jlb.3HI0715-305R
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Myeloid‐derived suppressor cells are immune‐suppressive cells that are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. As myeloid‐derived suppressor cells inhibit anti‐tumor immunity and promote tumor progression, we are determining how their viability is regulated. Previous studies have established that the damage‐associated molecular pattern molecule high‐mobility group box protein 1 drives myeloid‐derived suppressor cell accumulation and suppressive potency and is ubiquitously present in the tumor microenvironment. As high‐mobility group box protein 1 also facilitates tumor cell survival by inducing autophagy, we sought to determine if high‐mobility group box protein 1 regulates myeloid‐derived suppressor cell survival through induction of autophagy. Inhibition of autophagy increased the quantity of apoptotic myeloid‐derived suppressor cells, demonstrating that autophagy extends the survival and increases the viability of myeloid‐derived suppressor cells. Inhibition of high‐mobility group box protein 1 similarly increased the level of apoptotic myeloid‐derived suppressor cells and reduced myeloid‐derived suppressor cell autophagy, demonstrating that in addition to inducing the accumulation of myeloid‐derived suppressor cells, high‐mobility group box protein 1 sustains myeloid‐derived suppressor cell viability. Circulating myeloid‐derived suppressor cells have a default autophagic phenotype, and tumor‐infiltrating myeloid‐derived suppressor cells are more autophagic, consistent with the concept that inflammatory and hypoxic conditions within the microenvironment of solid tumors contribute to tumor progression by enhancing immune‐suppressive myeloid‐derived suppressor cells. Overall, these results demonstrate that in addition to previously recognized protumor effects, high‐mobility group box protein 1 contributes to tumor progression by increasing myeloid‐derived suppressor cell viability by driving them into a proautophagic state.