The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Morphologic Evidence of Anti-Tumor Specificity of T Cells Activated by Denritic Cells Derived from Peripheral Blood Mononuclear Cells of Thyroid Cancer Patients

  • Lee, Dae-Heui (Department of Pharmacology, Kosin University College of Medicine)
  • Received : 2012.04.16
  • Accepted : 2012.06.11
  • Published : 2012.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

Recent studies suggest that immunization with autologous dendritic cells (DCs) results in protective immunity and rejection of established tumors in various human malignancies. The purpose of this study is to determine whether DCs are generated from peripheral blood mononuclear cells (PBMNs) by using cytokines such as F1t-3 ligand (FL), granulocyte macrophage-colony stimulating factor (GM-CSF), IL-4, and TNF-${\alpha}$, and whether cytotoxic T cells activated against the thyroid cancer tissues by the DCs. Peripheral blood was obtained from 2 patients with thyroid cancer. DCs were established from PBMNs by culturing in the presence of FL, GM-CSF, IL-4, and TNF-${\alpha}$ for 14 days. At day 14, the differentiated DCs was analyzed morphologically. The immunophenotypic features of DCs such as CDla, CD83, and CD86 were analyzed by immunofluorelescence microscopy. At day 18, DCs and T cells were incubated with thyroid cancer tissues or normal thyroid tissues for additional 4 days, respectively. DCs generated from the PBMNs showed the typical morphology of DCs. Activated cytotoxic T lymphocytes (CTLs) were observed also. DCs and the CTLs were attached to the cancer tissues on scanning electron microscope. The DCs activated the CTLs, which able to specifically attack the thyroid cancer. This study provides morphologic evidence that the coculture of T cells/cancer tissues activated the T cells and differentiated CTLs. The CTLs tightly adhered to cancer tissues and lysed cancer tissues vigorously. Therefore DCs could be used as potential vaccines in the immunotherapy.

Keywords

References

  1. Steinman RM. The dendritic cell system and its role in immunogenicity. Ann Rev Immunol. 1991;9:271-296. https://doi.org/10.1146/annurev.iy.09.040191.001415
  2. Lee DH, Park JS, Eo WK, Kim WM, Kang K. Differentiation induction of dendritic cell phenotypes from human leukemic cell lines. Korean J Physiol Pharmacol. 2001;5:79-86.
  3. McKenna HJ, de Vries P, Brasel K, Lyman SD, Williams DE. Effect of flt3 ligand on the ex vivo expansion of human CD34+ hematopoietic progenitor cells. Blood. 1995;86:3413-3420.
  4. Young JC, Varma A, Digiusto D, Backer MP. Retention of quiescent hematopoietic cells with high proliferative potential during ex vivo stem cell culture. Blood. 1996;87:545-556.
  5. Piacibello W, Sanavio F, Garetto L, Severino A, Bergandi D, Ferrario J, Fagioli F, Berger M, Aglietta M. Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood. Blood. 1997;89:2644-2653.
  6. Lyman SD, James L, Johnson L, Brasel K, de Vries P, Escobar SS, Downey H, Splett RR, Beckmann MP, McKenna HJ. Cloning of the human homologue of the murine flt3 ligand: a growth factor for early hematopoietic progenitor cells. Blood. 1994;83:2795-2801.
  7. Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998;395:82-86. https://doi.org/10.1038/25764
  8. Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285:221-227 https://doi.org/10.1126/science.285.5425.221
  9. Lanzavecchia A, Lezzi G, Viola A. From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell. 1999; 96:1-4. https://doi.org/10.1016/S0092-8674(00)80952-6
  10. Lanzavecchia A, Sallusto F. Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol. 2001;2:487-492.
  11. Pardoll DM. Cancer vaccines. Nat Med. 1998;4 5 Suppl:525-531. https://doi.org/10.1038/nm0598supp-525
  12. Ockert D, Schmitz M, Hampl M, Rieber EP. Advances in cancer immunotherapy. Today. 1999;20:63-65.
  13. Nestle FO, Burg G, Dummer R. New perspectives on immunobiology and immunotherapy of melanoma. Immunol Today. 1999;20:5-7. https://doi.org/10.1016/S0167-5699(98)01373-5
  14. Steinman RM. Dendritic cells and immune-based therapies. Exp Hematol. 1996;24:859-862.
  15. Schuler G, Steinman RM. Dendritic cells as adjuvants for immune-mediated resistance to tumors. J Exp Med. 1997;186:1183-1187. https://doi.org/10.1084/jem.186.8.1183
  16. Lotze MT. Getting to the source: dendritic cells as therapeutic reagents for the treatment of patients with cancer. Ann Surg. 1997;226:1-5. https://doi.org/10.1097/00000658-199707000-00001
  17. Colaco CA. DC-based cancer immunotherapy: the sequel. Immunol Today. 1999;20:197-198. https://doi.org/10.1016/S0167-5699(98)01407-8
  18. Bottomly K. T cells and dendritic cells get intimate. Science. 1999;283:1124-1125. https://doi.org/10.1126/science.283.5405.1124
  19. Lee DH. Dendritic Cells-based vaccine and immune monitoring for hepatocellular carcinoma. Korean J Physiol Pharmacol. 2010;14:11-14. https://doi.org/10.4196/kjpp.2010.14.1.11

Cited by

  1. The role of the inflammatory microenvironment in thyroid carcinogenesis vol.21, pp.3, 2012, https://doi.org/10.1530/erc-13-0431