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

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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.

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Authors and Affiliations

  1. Department of Immunology, Nankai University School of Medicine, Nankai University, 300071, Tianjin, China

    Yu Liu, Yinyan Yu, Suguang Yang, Bin Zeng, Zhuohan Zhang, Guohui Jiao, Yuan Zhang, Limin Cai & Rongcun Yang

  2. Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, 300071, Tianjin, China

    Yu Liu, Yinyan Yu, Suguang Yang, Bin Zeng, Zhuohan Zhang, Guohui Jiao, Yuan Zhang, Limin Cai & Rongcun Yang

Authors
  1. Yu Liu
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  2. Yinyan Yu
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  4. Bin Zeng
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  7. Yuan Zhang
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  9. Rongcun Yang
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Correspondence to Rongcun Yang.

Additional information

This research was supported by Nankai University grant, NSFC grant “30771967”, “985” grant,The Ministry of Science and Technology grant “2006AA020502”“06C26211200695”, Tianjin Grant “07JCZDJC03300” and “06ZHCXSH04800”.

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Liu, Y., Yu, Y., Yang, S. et al. Regulation of arginase I activity and expression by both PD-1 and CTLA-4 on the myeloid-derived suppressor cells. Cancer Immunol Immunother 58, 687–697 (2009). https://doi.org/10.1007/s00262-008-0591-5

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  • DOI: https://doi.org/10.1007/s00262-008-0591-5

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