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

Gang Xiao, Xuanjun Wang, Jun Sheng, Shengjun Lu, Xuezhong Yu, Jennifer D. Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number13
JournalJournal of Hematology and Oncology
Volume8
Issue number1
DOIs
StatePublished - 2015

Keywords

  • MDSC
  • Macrophage
  • NKG2D
  • Soluble MIC
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

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