DOI QR코드

DOI QR Code

Tumor-derived CD4+CD25+ Tregs Inhibit the Maturation and Antigen-Presenting Function of Dendritic Cells

  • Du, Yong (Department of Pediatrics, First Affiliated Hospital of Wenzhou Medical University) ;
  • Chen, Xin (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University) ;
  • Lin, Xiu-Qing (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University) ;
  • Wu, Wei (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University) ;
  • Huang, Zhi-Ming (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University)
  • Published : 2015.04.14

Abstract

CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue response and maintenance of self-tolerance. Studies have found Tregs could suppress tumor-specific T cell-mediated immune response and promote cancer progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells (DCs) are professional antigen-presenting cells and capable of activating antigen-specific immune responses, which make them ideal candidate for cancer immunotherapy. Now various DC vaccines are considered as effective treatment for cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice with hepatocellular carcinoma and investigate the interaction between tumor-derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory molecule expression on splenic DCs, even in the presence of Teff cells and simultaneously inhibited IL-12 and $TNF-{\alpha}$ secretion by DCs.

Keywords

CD4+CD25+regulatory T cell;dendritic cell;costimulatory molecule;immunoregulation

References

  1. Ahmed Ali HA, Di J, Mei W, et al (2014). Antitumor activity of lentivirus-mediated interleukin-12 gene modified dendritic cells in human lung cancer in vitro. Asian Pac J Cancer Prev, 15, 611-6. https://doi.org/10.7314/APJCP.2014.15.2.611
  2. Auray G, Facci MR, van Kessel J, et al (2010). Differential activation and maturation of two porcine DC population follow TLR ligand stimulation. Mol Immunol, 47, 2103-11. https://doi.org/10.1016/j.molimm.2010.03.016
  3. Bonifaz L, Bonnyay D, Mahnke K, et al (2002). Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class Iproducts and peripheral CD8+ T cell tolerance. J Exp Med, 196, 1627-38. https://doi.org/10.1084/jem.20021598
  4. Cabrera R, Ararat M, Eksioglu EA, et al (2010). Influence of serum and soluble CD25 (sCD25) on regulatory and effector T cell function in hepatocellular carcinoma. Scand J Immunol, 72, 293-301. https://doi.org/10.1111/j.1365-3083.2010.02427.x
  5. Corthay A (2009). How do regulatory T cells work? Scand J Immunol, 70, 326-36. https://doi.org/10.1111/j.1365-3083.2009.02308.x
  6. Forner A, Llovet JM, Bruix J (2012). Hepatocellular carcinoma. Lancet, 379, 1245-55. https://doi.org/10.1016/S0140-6736(11)61347-0
  7. Fu T, Zhang P, Feng L, et al (2011). Accelerated acute allograft rejection accompanied by enhanced T-cell proliferation and attenuated treg function in RBP-J deficient mice. Mol Immunol, 48, 751-9. https://doi.org/10.1016/j.molimm.2010.11.016
  8. Herman S, Krenbek D, Klimas M, et al (2012). Regulatory T cells form stable and long-lasting cell cluster with myeloid dendritic cells (DC). Int Immunol, 24, 417-26. https://doi.org/10.1093/intimm/dxs039
  9. Hu JL, Yang Z, Tang JR, et al (2013). Effects of gastric cancer cells on the differentiation of Treg cells. Asian Pac J Cancer Prev, 14, 4607-10 https://doi.org/10.7314/APJCP.2013.14.8.4607
  10. Hu YX, Li M, Jia XH, et al (2013). HPV16 CTL epitope peptide-activated dendritic cell and natural killer co-culture for therapy of cervical cancer in an animal model. Asian Pac J Cancer Prev, 14, 7335-8 https://doi.org/10.7314/APJCP.2013.14.12.7335
  11. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistices. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  12. Kohl J, Wills-Karp M (2007). Complement regulates inhalation tolerance at the dendritic cell/T cell interface. Mol Immunol, 44, 44-56. https://doi.org/10.1016/j.molimm.2006.06.016
  13. Liu Z, Kim JH, Falo LD Jr, et al (2009). Tumor regulatory T cells potently abrogate antitumor immunity. J Immunol, 182, 6160-7. https://doi.org/10.4049/jimmunol.0802664
  14. Onishi Y, Fehervari Z, Yamaguchi T, et al (2008). Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. PNAS, 105, 10113-8. https://doi.org/10.1073/pnas.0711106105
  15. Ramanathan P, Ganeshrajah S, Kamalalayam R, et al (2014). Development and clinical evaluation of dendritic cell vaccines for HPV related cervical cancer- a feasibility study. Asian Pac J Cancer Prev, 15, 5909-16 https://doi.org/10.7314/APJCP.2014.15.14.5909
  16. Shen Z, Zhou S, Wang Y, et al (2010). Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer. J Cancer Res Clin Oncol, 136, 1585-95. https://doi.org/10.1007/s00432-010-0816-9
  17. Unitt E, Rushbrook SM, Marshall A, et al (2005). Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatol, 41, 722-30. https://doi.org/10.1002/hep.20644
  18. Wan WJ, Tao Z, Gu W, et al (2013). Variation of blood T lymphocyte subgroups in patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4671-3. https://doi.org/10.7314/APJCP.2013.14.8.4671
  19. Zhan HL, Gao X, Zhou XF, et al (2012). Presence of tumour-infiltrating foxp3+ lymphocytes correlates with immature tumour angiogenesis in renal cell carcinomas. Asian Pac J Cancer Prev, 13, 867-72. https://doi.org/10.7314/APJCP.2012.13.3.867

Cited by

  1. Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer vol.14, pp.1, 2017, https://doi.org/10.3892/etm.2017.4562
  2. The immune system in cancer metastasis: friend or foe? vol.5, pp.1, 2017, https://doi.org/10.1186/s40425-017-0283-9
  3. Helicobacter pylori infection and inflammatory bowel disease: a crosstalk between upper and lower digestive tract vol.9, pp.10, 2018, https://doi.org/10.1038/s41419-018-0982-2
  4. Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer vol.19, pp.1, 2019, https://doi.org/10.1186/s12885-019-5320-2