CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer Academic Article uri icon

abstract

  • Myeloid-derived suppressor cells (MDSCs) are a prominent component of the pro-tumoral response. The phenotype of and mechanisms used by MDSCs is heterogeneous and requires more precise characterization in gastric cancer (GC) patients. Here, we have identified a novel subset of CD45+CD33lowCD11bdim MDSCs in the peripheral blood of GC patients compared to healthy individuals. CD45+CD33lowCD11bdim MDSCs morphologically resembled neutrophils and expressed high levels of the neutrophil marker CD66b. Circulating CD45+CD33lowCD11bdim MDSCs effectively suppressed CD8+ T cells activity through the inhibition of CD8+ T cell proliferation and interferon-γ (IFN-γ) and granzyme B (GrB) production. The proportion of CD45+CD33lowCD11bdim MDSCs also negatively correlated with the proportion of IFN-γ+CD8+ T cell in the peripheral blood of GC patients. GC patient serum-derived IL-6 and IL-8 activated and induced CD45+CD33lowCD11bdim MDSCs to express arginase I via the PI3K-AKT signaling pathway. This pathway contributed to CD8+ T cell suppression as it was partially rescued by the blockade of the IL-6/IL-8-arginase I axis. Peripheral blood CD45+CD33lowCD11bdim MDSCs, as well as IL-6, IL-8, and arginase I serum levels, positively correlated with GC progression and negatively correlated with overall patient survival. Altogether, our results highlight that a subset of neutrophilic CD45+CD33lowCD11bdim MDSCs is functionally immunosuppressive and activated via the IL-6/IL-8-arginase I axis in GC patients.

authors

  • Mao, Fang-yuan
  • Zhao, Yong-liang
  • Lv, Yi-pin
  • Teng, Yong-sheng
  • Kong, Hui
  • Liu, Yu-gang
  • Wu, Xiao-long
  • Hao, Chuan-jie
  • Chen, Weisan
  • Duan, Mu bing
  • Han, Bin
  • Ma, Qiang
  • Wang, Ting-ting
  • Peng, Liu-sheng
  • Zhang, Jin-yu
  • Cheng, Ping
  • Su, Chong-yu
  • Fu, Xiao-long
  • Zou, Quan-ming
  • Guo, Gang
  • Guo, Xiao-lan
  • Zhuang, Yuan

publication date

  • 2018

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