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Investigation on the effects of soluble programmed death-1 (sPD-1) enhancing anti-tumor immune response

  • Yuan Ye
  • He Yufei
  • Wang Xiaohong
  • Zhang Hui
  • Li Dong
  • Feng Zuohua
  • Zhang Guimei
Article

Summary

By using semi-quantitative RT-PCR method, it was found that PD-L1 mRNA but not PD-L2 mRNA was expressed in H22 hepatoma cells and both PD-L1 and PD-L2 mRNAs were expressed in tumor tissues of tumor-bearing mice and upregulated as compared with muscle tissues in normal mice and H22 hepatoma cells. PD-L1 and PD-L2 were also expressed on the surface of the activated T cells. The soluble recombinant sPD-1 expressed from the constructed eukaryotic expression vector could enhance the lysis of tumor cells by lymphocytes stimulated specifically with antigen. The expression of sPD-1 by local gene therapy on the inoculation site of H22 hepatoma cells could inhibit the growth of tumor. The results of this study indicate that expression of soluble receptor of negative costimulatory molecules could reduce the inhibitory effect on T cells in tumor microenvironment and enhance the cytotoxicity of T cells on tumor cells. This possibly provides a new method of improving efficacy of tumor gene therapy.

Key words

PD-1 Immune tolerance Hepatocarcinoma Soluble receptor Gene therapy 

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References

  1. 1.
    Freeman G J, Long A J, Iwai Yet al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med, 2000, 192:1027PubMedCrossRefGoogle Scholar
  2. 2.
    Latchman Y, Wood C R, Chernova Tet al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol, 2001, 2:261PubMedCrossRefGoogle Scholar
  3. 3.
    Dong H, Strome S E, Salomao D Ret al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med, 2002, 8:793PubMedGoogle Scholar
  4. 4.
    Wai Y, Ishida M, Tanaka Yet al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA, 2002, 99:12293CrossRefGoogle Scholar
  5. 5.
    Feng Z H, Huang B, Zhang G Met al. Investigation on the effect of peptides mixture from tumor cells inducing anti-tumor specific immune response. Science China (Series C, Chinese), 2002, 45:361CrossRefGoogle Scholar
  6. 6.
    Mourich D V, Munks M W, Murphy J Cet al. Spermine compaction is an efficient and economical method of producing vaccination-grade DNA. J Immunol Methods, 2003, 274:257PubMedCrossRefGoogle Scholar
  7. 7.
    Greenwald R J, Latchman Y E, Sharpe A H. Negative co-receptors on lymphocytes. Curr Opin Immunol, 2002, 14:391PubMedCrossRefGoogle Scholar
  8. 8.
    Strome S E, Dong H, Tamura Het al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res, 2003, 63:6501PubMedGoogle Scholar
  9. 9.
    Wintterle S, Schreiner B, Mitsdoerffer Met al. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res, 2003, 63:7462PubMedGoogle Scholar
  10. 10.
    Curiel T J, Wei S, Dong Het al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med, 2003, 9:562PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2004

Authors and Affiliations

  • Yuan Ye
    • 1
  • He Yufei
    • 1
  • Wang Xiaohong
    • 1
  • Zhang Hui
    • 1
  • Li Dong
    • 1
  • Feng Zuohua
    • 1
  • Zhang Guimei
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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