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http://dx.doi.org/10.7314/APJCP.2015.16.2.571

Dendritic Cells Induce Specific Cytotoxic T Lymphocytes against Prostate Cancer TRAMP-C2 Cells Loaded with Freeze-thaw Antigen and PEP-3 Peptide  

Liu, Xiao-Qi (Molecular Medicine and Cancer Research Center, Department of Biochemistry and Molecular Biology, Chongqing Medical University)
Jiang, Rong (Department of Stem Cell and Tissue Engineering, Chongqing Medical University)
Li, Si-Qi (Molecular Medicine and Cancer Research Center, Department of Biochemistry and Molecular Biology, Chongqing Medical University)
Wang, Jing (Molecular Medicine and Cancer Research Center, Department of Biochemistry and Molecular Biology, Chongqing Medical University)
Yi, Fa-Ping (Molecular Medicine and Cancer Research Center, Department of Biochemistry and Molecular Biology, Chongqing Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.2, 2015 , pp. 571-578 More about this Journal
Abstract
Prostate cancer is the most common cancer in men. In this study, we investigated immune responses of cytotoxic T lymphocytes (CTLs) against TRAMP-C2 prostate cancer cells after activation by dendritic cells (DCs) loaded with TRAMP-C2 freeze-thaw antigen and/or PEP-3 peptide in vitro. Bone marrow-derived DC from the bone marrow of the C57BL/6 were induced to mature by using the cytokine of rhGM-CSF and rhIL-4, and loaded with either the freeze-thaw antigen or PEP-3 peptide or both of them. Maturation of DCs was detected by flow cytometry. The killing efficiency of the CTLs on TRAMP-C2 cells were detected by flow cytometry, CCK8, colony formation, transwell migration, and wound-healing assay. The levels of the IFN-${\gamma}$, TNF-${\beta}$ and IL-12 were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the unloaded DCs, the loaded DCs had significantly increased expression of several phenotypes related to DC maturation. CTLs activated by DCs loaded with freeze-thaw antigen and PEP-3 peptide had more evident cytotoxicity against TRAMP-C2 cells in vitro. The secretion levels of IFN-${\gamma}$, TNF-${\beta}$ and IL-12, secreted by DCs loaded with antigen and PEP-3 and interaction with T cells, were higher than in the other groups. Our results suggest that the CTLs activated by DCs loaded with TRAMP-C2 freeze-thaw antigen and PEP-3 peptide exert a remarkable killing efficiency against TRAMP-C2 cells in vitro.
Keywords
Dendritic cells; prostate cancer; tramp-c2; cytotoxic t lymphocyte; immunotherapy;
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1 Bolhassani A, Safaiyan S, Rafati S (2011). Improvement of different vaccine delivery systems for cancer therapy. Mol Cancer, 10, 3.
2 Chiang CL, Benencia F, Coukos G (2010). Whole tumor antigen vaccines. Semin Immunol, 22, 132-43.   DOI
3 Chiang CL, Hagemann AR, Leskowitz R, et al (2011). Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses. PLoS One, 6, 28732.   DOI
4 Clive KS, Tyler JA, Clifton GT, et al (2012). The GP2 peptide: A HER2/neu-based breast cancer vaccine. J Surg Oncol, 105, 452-8.   DOI
5 Drake CG (2010). Prostate cancer as a model for tumor immunotherapy. Nat Rev Immunol, 10, 580-93.   DOI   ScienceOn
6 Furnari FB, Huang HJ, Cavenee WK (1996). Molecular biology of malignant degeneration of astrocytoma. Pediatr Neurosurg, 24, 41-9.   DOI
7 Guo K, Liu CX (2010). Research progress on the serum markers of prostate cancer. J Practical Med, 26, 3465-6.
8 Gilboa E, Nair SK, Lyerly HK (1998). Immunotherapy of cancer with dendritic-cell-based vaccines. Immunother, 46, 82-7.   DOI
9 Hong Ge, Xiaoqi Gong, Careen K (2002). Evidence of high incidence of EGFRvIII expression and coexpression with EGFR in human invasive breast cancer by laser capture microdissection and immunohistochemical analysis. Int J Cancer, 98, 357-61.   DOI
10 Heimberger AB, Crotty LE, Archer GE, et al (2003). Epidermal growth factor receptor variant VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res, 11, 4247-54.
11 Inaba K, Inaba M, Romani N, et al (1992). Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colonystimulating factor. J Exp Med, 176, 1693-702.   DOI
12 Jacques Ferlay, Hai-Rim Shin, Freddie Bray, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.   DOI
13 Kreiter S, Diken M, Selmi A, et al (2011). Tumor vaccination using messenger RNA: prospects of a future therapy. Curr Opin Immunol, 23, 399-406.   DOI
14 Kang TH, Mao CP, La V, Chen A, et al (2013). Innovative DNA vaccine to break immune tolerance against tumor self-antigen. Hum Gene Ther, 24, 181-8.   DOI
15 Lee HJ, Hong CY, Kim MH, et al (2012). In vitro induction of anterior gradient-2-specific cytotoxic T lymphocytes by dendritic cells transduced with recombinant adenoviruses as a potential therapy for colorectal cancer. Exp Mol Med, 44, 60-7.   DOI
16 Lorenzi S, Mattei F, Sistigu A, et al (2011). Type I IFNs control antigen retention and survival of CD8a (+) dendritic cells after uptake of tumor apoptotic cells leading tocrosspriming. J Immunol, 186, 5142-50.   DOI
17 Long JR, Xiong F, Dong ZQ (2010). Research progress on multiple drug resistance of prostate cancer. Guangdong Med J, 31, 2871-3.
18 McDonnell AM, Prosser AC, Van Bruggen I, et al (2010). CD8alpha+DC are not the sole subset cross-presenting cell-associated tumor antigens from a solid tumor. Eur J Immunol, 40, 1617-27.   DOI
19 Matera L (2011). The choice of the antigen in the dendritic cell-based vaccine therapy for prostate cancer. Cancer Treat Rev, 36, 131-41.
20 Morandi F, Chiesa S, Bocca P, et al (2006). Tumor mRNAtransfected dendritic cells stimulate the generation of CTL that recognize neuroblastoma-associated antigens and kill tumor cells: immunotherapeutic implications. Neoplasia, 10, 833-42.
21 Siegel R, Naishadham D, Jemal A (2012). Cancer statistics. CA Cancer J Clin, 62, 10-29.   DOI   ScienceOn
22 Park MH, Yang DH, Kim MH, et al (2011). Alpha-Type 1 polarized dendritic cells loaded with apoptotic allogeneic breast cancer cells can induce potent cytotoxic T lymphocytes against breast cancer. Cancer Res Treat, 43, 56-66.   DOI
23 Quintarelli C, Dotti G, Hasan ST, et al (2011). High-avidity cytotoxic-T-lymphocytes specific for a new preferentially expressed antigen of melanoma (PRAME)-derived peptide can target leukemic- and leukemic-precursor cells. Blood, 117, 3353-62.   DOI
24 Roupret M, Zigeuner R, Palou J, et al (2011). European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol, 59, 584-94.   DOI   ScienceOn
25 Stockwin LH, McGonagle D, Martin IG, et al (2000). Dendritic cells immunological sentinels with a central role in health and disease. Immunol Cell Biol, 78, 91-102.   DOI
26 Timothy R, Susan S, Bao-Li Chang, et al (2013). Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of African descent. Prostate Cancer, 2013, 1-12.
27 Tel J, Schreibelt G, Sittig SP, et al (2013). Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets. Blood, 121, 459-67.   DOI
28 Yi XM, Zhou WQ (2010). Epigenetics of prostate cancer. National J Androl, 16, 635-41.
29 Yiin JJ, Hu B, Schornack PA, Sengar RS, et al (2010). ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain. Mol Cancer Ther, 9, 929-41.   DOI
30 Yang DH, Kim MH, Hong CY, et al (2010). Alpha-type 1-polarized dendritic cells loaded with apoptotic allogeneic myeloma cell line induce strong CTL responses against autologous myeloma cells. Ann Hematol, 89, 795-801.   DOI