DOI QR코드

DOI QR Code

Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model: Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC

  • Baek, Soyoung (Office of Biomedical Professors, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Seog Jae (Department of Thoracic & Cardiovascular Surgery, Jeju National University School of Medicine) ;
  • Kim, Myoung Joo (Office of Biomedical Professors, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Hyunah (Office of Biomedical Professors, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2012.11.06
  • Accepted : 2012.11.27
  • Published : 2012.12.31

Abstract

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either $CD34^+$ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-${\beta}$ secretion were higher in SDC but CCR7 expression, IFN-${\gamma}$ and IL-10 secretion were higher in MoDC. The proportion of $CD11c^+CD8a^+$ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-${\gamma}$ secreting $CD8^+$ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.

Keywords

Acknowledgement

Supported by : Korean Ministry of Knowledge Economy, Samsung Biomedical

References

  1. Steinman, R. M. 1991. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9: 271-296. https://doi.org/10.1146/annurev.iy.09.040191.001415
  2. Banchereau, J. and R. M. Steinman. 1998. Dendritic cells and the control of immunity. Nature 392: 245-252. https://doi.org/10.1038/32588
  3. Paglia, P., C. Chiodoni, M. Rodolfo, and M. P. Colombo. 1996. Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo. J. Exp. Med. 183: 317-322. https://doi.org/10.1084/jem.183.1.317
  4. Palucka, K. and J. Banchereau. 1999. Dendritic cells: a link between innate and adaptive immunity. J. Clin. Immunol. 19:12-25. https://doi.org/10.1023/A:1020558317162
  5. Paczesny, S., J. Banchereau, K. M. Wittkowski, G. Saracino, J. Fay, and A. K. Palucka. 2004. Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. J. Exp. Med. 199: 1503-1511. https://doi.org/10.1084/jem.20032118
  6. Kim, J. H., Y. Lee, Y. S. Bae, W. S. Kim, K. Kim, H. Y. Im, W. K. Kang, K. Park, H. Y. Choi, H. M. Lee, S. Y. Baek, H. Lee, H. Doh, B. M. Kim, C. Y. Kim, C. Jeon, and C. W. Jung. 2007. Phase I/II study of immunotherapy using autologous tumor lysate-pulsed dendritic cells in patients with metastatic renal cell carcinoma. Clin. Immunol. 125: 257-267. https://doi.org/10.1016/j.clim.2007.07.014
  7. Baek, S., C. S. Kim, S. B. Kim, Y. M. Kim, S. W. Kwon, Y. Kim, H. Kim, and H. Lee. 2011. Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial. J. Transl. Med. 9: 178. https://doi.org/10.1186/1479-5876-9-178
  8. Ragde, H., W. A. Cavanagh, and B. A. Tjoa. 2004. Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer. J. Urol. 172: 2532-2538. https://doi.org/10.1097/01.ju.0000144211.51111.e4
  9. Iwashita, Y., K. Tahara, S. Goto, A. Sasaki, S. Kai, M. Seike, C. L. Chen, K. Kawano, and S. Kitano. 2003. A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Cancer Immunol. Immunother. 52: 155-161.
  10. Hirschowitz, E. A., T. Foody, R. Kryscio, L. Dickson, J. Sturgill, and J. Yannelli. 2004. Autologous dendritic cell vaccines for non-small-cell lung cancer. J. Clin. Oncol. 22: 2808-2815. https://doi.org/10.1200/JCO.2004.01.074
  11. Hege, K. M. and D. P. Carbone. 2003. Lung cancer vaccines and gene therapy. Lung Cancer 41 Suppl 1: S103-113.
  12. Fong, L., Y. Hou, A. Rivas, C. Benike, A. Yuen, G. A. Fisher, M. M. Davis, and E. G. Engleman. 2001. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc. Natl. Acad. Sci. U.S.A. 98: 8809-8814. https://doi.org/10.1073/pnas.141226398
  13. Parkin, D. M., F. Bray, J. Ferlay, and P. Pisani. 2005. Global cancer statistics, 2002. CA Cancer J. Clin. 55: 74-108. https://doi.org/10.3322/canjclin.55.2.74
  14. Spira, A. and D. S. Ettinger. 2004. Multidisciplinary management of lung cancer. N. Engl. J. Med. 350: 379-392. https://doi.org/10.1056/NEJMra035536
  15. Lee, S. J., M. J. Kim, S. H. In, S. Baek, and H. Lee. 2005. Immunocell therapy for lung cancer: dendritic cell based adjuvant therapy in mouse lung cancer model. Immune Netw. 5: 36-44. https://doi.org/10.4110/in.2005.5.1.36
  16. Ward, K. A., L. A. Stewart, and A. P. Schwarer. 2006. CD34+-derived CD11c+++ BDCA-1++ CD123++ DC: expansion of a phenotypically undescribed myeloid DC1 population for use in adoptive immunotherapy. Cytotherapy 8: 130-140. https://doi.org/10.1080/14653240600620689
  17. Encabo, A., P. Solves, E. Mateu, P. Sepúlveda, F. Carbonell- Uberos, and M. D. Miñana. 2004. Selective generation of different dendritic cell precursors from CD34+ cells by interleukin-6 and interleukin-3. Stem Cells 22: 725-740. https://doi.org/10.1634/stemcells.22-5-725
  18. Guo, G., S. Chen, J. Zhang, L. Luo, J. Yu, H. Dong, H. Xu, Z. Su, and L. Wu. 2005. Antitumor activity of a fusion of esophageal carcinoma cells with dendritic cells derived from cord blood. Vaccine 23: 5225-5230. https://doi.org/10.1016/j.vaccine.2005.07.080
  19. Xu, R. L., Y. Tang, P. L. Ogburn, K. Malinowski, S. Madajewicz, F. Santiago-Schwarz, and Q. Fan. 2004. Implication of delayed TNF-alpha exposure on dendritic cell maturation and expansion from cryopreserved cord blood CD34+ hematopoietic progenitors. J. Immunol. Methods 293: 169-182. https://doi.org/10.1016/j.jim.2004.08.001
  20. Baleeiro, R. B., L. B. Anselmo, F. A. Soares, C. A. Pinto, O. Ramos, J. L. Gross, F. Haddad, R. N. Younes, M. Y. Tomiyoshi, P. C. Bergami-Santos, and J. A. Barbuto. 2008. High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer. Cancer Immunol. Immunother. 57: 1335-1345. https://doi.org/10.1007/s00262-008-0468-7
  21. Hirschowitz, E. A., T. Foody, G. E. Hidalgo, and J. R. Yannelli. 2007. Immunization of NSCLC patients with antigen- pulsed immature autologous dendritic cells. Lung Cancer 57: 365-372. https://doi.org/10.1016/j.lungcan.2007.04.002
  22. Moser, M. and K. M. Murphy. 2000. Dendritic cell regulation of TH1-TH2 development. Nat. Immunol. 1: 199-205.
  23. Martín, P., G. M. del Hoyo, F. Anjuère, S. R. Ruiz, C. F. Arias, A. R. Marín, and C. Ardavín. 2000. Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8alpha(−) and CD8alpha(+) dendritic cells are generated from CD4(low) lymphoid-committed precursors. Blood 96:2511-2519.

Cited by

  1. Immunotherapy of DC-CIK cells enhances the efficacy of chemotherapy for solid cancer: a meta-analysis of randomized controlled trials in Chinese patients vol.16, pp.9, 2012, https://doi.org/10.1631/jzus.b1500003
  2. Irradiation enhances dendritic cell potential antitumor activity by inducing tumor cell expressing TNF-α vol.34, pp.3, 2017, https://doi.org/10.1007/s12032-016-0864-3
  3. Antitumor Vaccines Based on Dendritic Cells: From Experiments using Animal Tumor Models to Clinical Trials vol.9, pp.3, 2012, https://doi.org/10.32607/20758251-2017-9-3-27-38
  4. Dendritic cell/cytokine‐induced killer cell‐based immunotherapy in lung cancer: What we know and future landscape vol.235, pp.1, 2020, https://doi.org/10.1002/jcp.28977