Soluble NKG2D ligand promotes MDSC expansion and skews macrophage to the alternatively activated phenotype

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• 作者：Gang Xiao (1) (4)
  Xuanjun Wang (2)
  Jun Sheng (2)
  Shengjun Lu (1) (5)
  Xuezhong Yu (1) (3)
  Jennifer D Wu (1) (3)
  
  1. Department of Microbiology and Immunology ; Medical University of South Carolina ; Charleston ; SC ; USA
  4. Present address ; The Third Hospital of South Medical University ; Guangzhou ; China
  2. Key Lab for Puer Tea Science ; Ministry of Education ; Yunnan Agricultural University ; Kunming ; China
  5. Present Address ; Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan ; China
  3. Cancer Immunology Program ; Hollings Cancer Center ; Charleston ; SC ; USA
  
• 关键词：NKG2D ; Soluble MIC ; MDSC ; Macrophage ; Tumor
• 刊名：Journal of Hematology & Oncology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：8
• 期：1
• 全文大小：1,652 KB
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• 刊物主题：Oncology; Hematology; Cancer Research;
• 出版者：BioMed Central
• ISSN：1756-8722

文摘

Expression of surface NKG2D ligand MIC on tumor cells is deemed to stimulate NK and co-stimulate CD8 T cell anti-tumor immunity. Human cancer cells however frequently adopt a proteinase-mediated shedding strategy to generate soluble MIC (sMIC) to circumvent host immunity. High levels of sMIC have been shown to correlate with advanced disease stages in cancer patients. The underlying mechanism is currently understood as systemic downregulation of NKG2D expression on CD8 T and NK cells and perturbing NK cell periphery maintenance. Herein we report a novel mechanism by which sMIC poses immune suppressive effect on host immunity and tumor microenvironment. We demonstrate that sMIC facilitates expansion of myeloid-derived suppressor cells (MDSCs) and skews macrophages to the more immune suppressive alternative phenotype through activation of STAT3. These findings further endorse that sMIC is an important therapeutic target for cancer immunotherapy.