Interactions between interleukin-6 and myeloid-derived suppressor cells drive the chemoresistant phenotype of hepatocellular cancer

摘要: Emerging evidence implicates an important role for myeloid-derived suppressor cells (MDSCs) in tumor growth, angiogenesis and metastasis. However, limited knowledge is known about the function of MDSCs response to chemotherapies. In this study, we find that drug-resistant hepatocellular cancer (HCC) cells-derived conditioned medium significantly enhances expansion immunosuppressive compared their parental sensitive cells, which demonstrated by increased level arginase, nitric oxide (NO), reactive oxygen species (ROS). Next, reveal HCC IL-6 activated MDSCs, using anti-IL-6 neutralizing antibody caused a reduced MDSC activity. More importantly, depletion via administration anti-Gr-1 or blockade signaling sensitized 5-FU-resistant H22 hepatoma chemotherapy immunocompetent C57BL/6N mice. primary human HCC, expression levels strongly correlate with phenotype patients. conclusion, these results describe drug resistance suggest MDSC-targeting treatments may be potential therapeutic strategy chemoresistance.