DOI QR코드

DOI QR Code

Expression and Clinical Significance of Myeloid Derived Suppressor Cells in Chronic Hepatitis B Patients

  • Lu, Li-Rong (Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Liu, Jing (Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Xu, Zhen (Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Zhang, Geng-Lin (Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University) ;
  • Li, De-Chang (Department of Infectious Diseases, The Second People's Hospital of North Guangdong) ;
  • Lin, Chao-Shuang (Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University)
  • Published : 2014.05.30

Abstract

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.

Keywords

References

  1. Bunt SK, Sinha P, Clements VK, et al (2006). Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol, 176, 284-90. https://doi.org/10.4049/jimmunol.176.1.284
  2. Cai W, Qin A, Guo P, et al (2013). Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol, 33, 798-808. https://doi.org/10.1007/s10875-012-9861-2
  3. Crawford A, Wherry EJ (2009). The diversity of costimulatory and inhibitory receptor pathways and the regulation of antiviral T cell responses. Curr Opin Immunol, 21, 179-86. https://doi.org/10.1016/j.coi.2009.01.010
  4. Dmitry I, Gabrilovich, Srinivas Nagaraj (2009). Myeloidderived-suppressor cells as regulators of the immune system. Nat Rev Immunol, 9, 162-74. https://doi.org/10.1038/nri2506
  5. European Association for the Study of the Liver (2012). EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatology, 57, 167-85. https://doi.org/10.1016/j.jhep.2012.02.010
  6. Gabrilovieh DI, Nagaraj S (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol, 9, 162-74. https://doi.org/10.1038/nri2506
  7. Greten TF, Manns MP, Korangy F,et al (2011). Myeloid derived suppressor cells in human diseases. Int Immunopharmacol, 11, 802-7. https://doi.org/10.1016/j.intimp.2011.01.003
  8. Hakan A, Ozturk O, Binnur K, et al (2013). Prevalence of common YMDD motif mutations in long term treated chronic HBV infections in a Turkish population. Asian Pac J Cancer Prev, 14, 5489-94. https://doi.org/10.7314/APJCP.2013.14.9.5489
  9. Ito K, Kim KH, Lok AS, et aL (2009). Characterization ofgenotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigenprecursor and identification offurin as the candidate enzyme. J Virol, 83, 3507-17. https://doi.org/10.1128/JVI.02348-08
  10. Lathers DM, Clark JI, Achille NJ, et al (2004). Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother, 53, 422-30. https://doi.org/10.1007/s00262-003-0459-7
  11. Li L, Wu B, Yang LB, et al (2013). Chronic hepatitis b virus infection and risk of pancreatic cancer: a meta-analysis. Asian Pac J Cancer Prev, 14, 275-9. https://doi.org/10.7314/APJCP.2013.14.1.275
  12. Lim YS, Han S, Heo NY, et al (2014). Liver Transplantation, and Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Treated with Entecavir vs Lamivudine. Gastroenterol, 25.
  13. Martin F, Apetoh L, Ghiringhelli F (2012). Role of myeloidderived suppressor cells in tumor immunotherapy. Immunotherapy, 4, 43-57. https://doi.org/10.2217/imt.11.154
  14. Milich D, Liang TJ (2003). Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology, 38, 1075-86. https://doi.org/10.1053/jhep.2003.50453
  15. Peranzoni E, Zilio S, Marigo I, et al (2010). Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol, 22, 238-44. https://doi.org/10.1016/j.coi.2010.01.021
  16. Qin A, Cai W, Pan T, et al (2013). Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositiveindividuals. J Virol, 87, 1477-90. https://doi.org/10.1128/JVI.01759-12
  17. Qu P, Boelte KC, Lin PC (2012). Negative regulation of myeloid-derived suppressor cells in cancer. Immunol Invest, 41, 562-80. https://doi.org/10.3109/08820139.2012.685538
  18. Revill P, Yuen L, Walsh R, et a1 (2010). Bioinformatic analysis of the hepadnavirus e-antigen and its precursor identifies remarkable sequence conservation in all orthohepadnaviruses. J Med Virol, 82, 104-15. https://doi.org/10.1002/jmv.21645
  19. Serafini P, Borrello I, Bronte V, et al (2006). Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol, 16, 53-65. https://doi.org/10.1016/j.semcancer.2005.07.005
  20. Suzuki E, Kapoor V, Jassar AS, et al (2005). Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res, 11, 6713-21. https://doi.org/10.1158/1078-0432.CCR-05-0883
  21. Tacke RS, Lee HC, Goh C, et al (2012). Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production ofreactive oxygenspecies. Hepatology, 55, 343-53. https://doi.org/10.1002/hep.24700
  22. Tinoco R, Alcalde V, Yang Y, et a1 (2009). Cell-intrinsic transforming growth factor-beta signaling mediates virusspecific CD8+T cell deletion and viral persistence in vivo. Immunity, 31, 145-57. https://doi.org/10.1016/j.immuni.2009.06.015
  23. Vollbrecht T, Stirner R, Tufman A, et al (2012). Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells. AIDS, 26, 31-7. https://doi.org/10.1097/QAD.0b013e3283558446
  24. Wang FS, Zhang Z (2009). Host immunity influences disease progression and antiviral efficacy in humansinfected with hepatitis B virus. Expert Rev Gastroenterol Hepatol, 3, 499-512. https://doi.org/10.1586/egh.09.50
  25. Yu M, Niu ZM, Wei YQ (2013). Effective response of the peritoneum microenvironment to peritoneal and systemic metastasis from colorectal carcinoma. Asian Pac J Cancer Prev, 14, 7289-94. https://doi.org/10.7314/APJCP.2013.14.12.7289

Cited by

  1. Chronic hepatitis B surface antigen seroclearance-related immune factors vol.47, pp.1, 2016, https://doi.org/10.1111/hepr.12726
  2. Granulocytic myeloid-derived suppressor cells suppress virus-specific CD8+ T cell responses during acute Friend retrovirus infection vol.14, pp.1, 2017, https://doi.org/10.1186/s12977-017-0364-3
  3. The Role of Myeloid-Derived Suppressor Cells in Viral Infection vol.30, pp.2, 2017, https://doi.org/10.1089/vim.2016.0125
  4. Significant Roles of Regulatory T Cells and Myeloid Derived Suppressor Cells in Hepatitis B Virus Persistent Infection and Hepatitis B Virus-Related HCCs vol.16, pp.2, 2015, https://doi.org/10.3390/ijms16023307