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Cancer Immunology, Immunotherapy

, Volume 58, Issue 5, pp 687–697 | Cite as

Regulation of arginase I activity and expression by both PD-1 and CTLA-4 on the myeloid-derived suppressor cells

  • Yu Liu
  • Yinyan Yu
  • Suguang Yang
  • Bin Zeng
  • Zhuohan Zhang
  • Guohui Jiao
  • Yuan Zhang
  • Limin Cai
  • Rongcun Yang
Original Article

Abstract

An elevated number of Gr-1+CD11b+ myeloid-derived suppression cells (MDSCs) has been described in mice and human bearing tumor and associated with immune suppression. Arginase I production by MDSCs in the tumor environment may be a central mechanism for immunosuppression and tumor evasion. In this study and before, we found that Gr-1+CD11b+ MDSCs from ascites and spleen of mice bearing ovarian 18D carcinoma express a high level of PD-1, CTLA-4, B7-H1 and CD80 while other co-stimulatory molecules, namely CD40, B7-DC and CD86 are not detected. Further studies showed that PD-1 and CTLA-4 on the Gr-1+CD11b+ MDSCs regulated the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules could significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results were also observed while their ligands B7-H1 and/or CD80 were blocked or silenced. Furthermore, CD80 deficiency also decreased the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduced the suppressive potential of PD-1+CTLA-4+MDSCs. Blockade of PD-1, CTLA-4 or both also slowed tumor growth and improved the survival rate of tumor-bearing mice. Thus, there may exist a coinhibitory and costimulatory molecules-based immuno-regulating wet among MDSCs.

Keywords

Myeloid derived suppressor cells Arginase I PD-1 CTLA-4 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Yu Liu
    • 1
    • 2
  • Yinyan Yu
    • 1
    • 2
  • Suguang Yang
    • 1
    • 2
  • Bin Zeng
    • 1
    • 2
  • Zhuohan Zhang
    • 1
    • 2
  • Guohui Jiao
    • 1
    • 2
  • Yuan Zhang
    • 1
    • 2
  • Limin Cai
    • 1
    • 2
  • Rongcun Yang
    • 1
    • 2
  1. 1.Department of Immunology, Nankai University School of MedicineNankai UniversityTianjinChina
  2. 2.Key Laboratory of Bioactive Materials, Ministry of EducationNankai UniversityTianjinChina

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