Issue
Sensitization of cisplatin resistant bladder tumor by combination of cisplatin treatment and co-culture of dendritic cells with apoptotic bladder cancer cells
Corresponding Author(s) : Zhuo Chen
Cellular and Molecular Biology,
Vol. 64 No. 10: Issue 10
Abstract
Dendritic cells (DCs) are a population of professional antigen presenting cells (APCs), serving as central regulators of adaptive immunity by presenting antigens. In addition, DCs play essential roles in the connection of the innate and adaptive immune responses. Recently, therapeutic vaccines turn out to become a viable therapeutic approach for immunotherapy of cancers. Here we report a dendritic cell-based vaccine strategy which could suppress the bladder tumor growth in vivo and improve the efficiency of chemotherapy. In this study, we investigate the antitumor effects of mature DCs induced by antigen loading in bladder tumor in vivo. We demonstrate the co-culture of cisplatin induced apoptotic human bladder cancer cell line, T24 cells with immature DCs could promote the maturation of DCs. Cisplatin and these activated DCs were reintroduced into mice bearing the T24 cisplatin resistant cells-derived tumor growth to activate or boost the immune response. Mice with iDCs co-cultured with apoptotic T24 (iDCs T24 Apo) cells injection effectively initiate a cytotoxic effect against tumor growth and improve the survival rates of mice compared with controls. Moreover, we observed injection of iDCs T24 apoptosis cells combined with cisplatin into mice with T24 cisplatin resistant cancer cells-derived tumor resulted in a statistically significant suppression of tumor growth compared with mice injected with PBS alone, cisplatin alone, iDCs, iDCs T24 Apo cells, cisplatin plus iDCs. This study provides a dendritic cell-based vaccine strategy which might reduce the risk of tumor recurrence and improve the efficiency of anti-chemoresistance of bladder cancer.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- References
- Mellman I. Dendritic cells: Master regulators of the immune response. Cancer Immunol Res 2013; 1:145-149.
- Mildner A, Jung S. Development and function of dendritic cell subsets. Immunity 2014; 40:642-656.
- Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31:563-604.
- Segura E. Review of mouse and human dendritic cell subsets. Methods Mol Biol 2016; 1423:3-15.
- Pearce EJ, Everts B. Dendritic cell metabolism. Nat Rev Immunol 2015; 15:18-29.
- Dalod M, Chelbi R, Malissen B, Lawrence T. Dendritic cell maturation: Functional specialization through signaling specificity and transcriptional programming. EMBO J 2014; 33:1104-1116.
- Tan JK, O'Neill HC. Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J Leukoc Biol 2005; 78:319-324.
- Dudek AM, Martin S, Garg AD, Agostinis P. Immature, Semi-Mature, and fully mature dendritic cells: Toward a DC-Cancer cells interface that augments anticancer immunity. Front Immunol 2013; 4:438.
- Reis ESC. Dendritic cells in a mature age. Nat Rev Immunol 2006; 6:476-483.
- Pathak SK, Skold AE, Mohanram V, Persson C, Johansson U, Spetz AL. Activated apoptotic cells induce dendritic cell maturation via engagement of Toll-like receptor 4 (TLR4), dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN), and beta2 integrins. J Biol Chem 2012; 287:13731-13742.
- Tran JJ, Lamichhane P, Karyampudi L, Knutson KL. Tumor-infiltrating dendritic cells in cancer pathogenesis. J Immunol 2015; 194:2985-2991.
- Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012; 12:265-277.
- Sabado RL, Bhardwaj N. Cancer immunotherapy: Dendritic-cell vaccines on the move. Nature 2015; 519:300-301.
- Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 2013; 39:38-48.
- Inzkirweli N, Guckel B, Sohn C, Wallwiener D, Bastert G, Lindner M. Antigen loading of dendritic cells with apoptotic tumor cell-preparations is superior to that using necrotic cells or tumor lysates. Anticancer Res 2007; 27:2121-2129.
- Cannon MJ, Goyne HE, Stone PJ, Macdonald LJ, James LE, Cobos E, et al. Modulation of p38 MAPK signaling enhances dendritic cell activation of human CD4+ Th17 responses to ovarian tumor antigen. Cancer Immunol Immunother 2013; 62:839-849.
- Zheng J, Liu Q, Yang J, Ren Q, Cao W, Yang J, et al. Co-culture of apoptotic breast cancer cells with immature dendritic cells: A novel approach for DC-based vaccination in breast cancer. Braz J Med Biol Res 2012; 45:510-515.
- Fry TJ, Shand JL, Milliron M, Tasian SK, Mackall CL. Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches. Cancer Immunol Immunother 2009; 58:1257-1264.
- Xie XF, Ding Q, Hou JG, Chen G. Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer. Genet Mol Res 2015; 14:7548-7555.
- Wang Y, Zheng N, Lu Z, Wu W, Wang L, Nakao A, et al. In vivo expansion of two distinct dendritic cells in mouse livers and its impact on liver immune regulation. Liver Transpl 2006; 12:1850-1861.
- Burgdorf SK. Dendritic cell vaccination of patients with metastatic colorectal cancer. Dan Med Bull 2010; 57:B4171.
- Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 2000; 191:423-434.
- Jiang J, Xie D, Zhang W, Xiao G, Wen J. Fusion of Hsp70 to Mage-a1 enhances the potency of vaccine-specific immune responses. J Transl Med 2013; 11:300.
- Goldszmid RS, Idoyaga J, Bravo AI, Steinman R, Mordoh J, Wainstok R. Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol 2003; 171:5940-5947.
- Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, et al. STING-Dependent cytosolic DNA sensing promotes Radiation-Induced type i Interferon-Dependent antitumor immunity in immunogenic tumors. Immunity 2014; 41:843-852.
References
References
Mellman I. Dendritic cells: Master regulators of the immune response. Cancer Immunol Res 2013; 1:145-149.
Mildner A, Jung S. Development and function of dendritic cell subsets. Immunity 2014; 40:642-656.
Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31:563-604.
Segura E. Review of mouse and human dendritic cell subsets. Methods Mol Biol 2016; 1423:3-15.
Pearce EJ, Everts B. Dendritic cell metabolism. Nat Rev Immunol 2015; 15:18-29.
Dalod M, Chelbi R, Malissen B, Lawrence T. Dendritic cell maturation: Functional specialization through signaling specificity and transcriptional programming. EMBO J 2014; 33:1104-1116.
Tan JK, O'Neill HC. Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J Leukoc Biol 2005; 78:319-324.
Dudek AM, Martin S, Garg AD, Agostinis P. Immature, Semi-Mature, and fully mature dendritic cells: Toward a DC-Cancer cells interface that augments anticancer immunity. Front Immunol 2013; 4:438.
Reis ESC. Dendritic cells in a mature age. Nat Rev Immunol 2006; 6:476-483.
Pathak SK, Skold AE, Mohanram V, Persson C, Johansson U, Spetz AL. Activated apoptotic cells induce dendritic cell maturation via engagement of Toll-like receptor 4 (TLR4), dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN), and beta2 integrins. J Biol Chem 2012; 287:13731-13742.
Tran JJ, Lamichhane P, Karyampudi L, Knutson KL. Tumor-infiltrating dendritic cells in cancer pathogenesis. J Immunol 2015; 194:2985-2991.
Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012; 12:265-277.
Sabado RL, Bhardwaj N. Cancer immunotherapy: Dendritic-cell vaccines on the move. Nature 2015; 519:300-301.
Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 2013; 39:38-48.
Inzkirweli N, Guckel B, Sohn C, Wallwiener D, Bastert G, Lindner M. Antigen loading of dendritic cells with apoptotic tumor cell-preparations is superior to that using necrotic cells or tumor lysates. Anticancer Res 2007; 27:2121-2129.
Cannon MJ, Goyne HE, Stone PJ, Macdonald LJ, James LE, Cobos E, et al. Modulation of p38 MAPK signaling enhances dendritic cell activation of human CD4+ Th17 responses to ovarian tumor antigen. Cancer Immunol Immunother 2013; 62:839-849.
Zheng J, Liu Q, Yang J, Ren Q, Cao W, Yang J, et al. Co-culture of apoptotic breast cancer cells with immature dendritic cells: A novel approach for DC-based vaccination in breast cancer. Braz J Med Biol Res 2012; 45:510-515.
Fry TJ, Shand JL, Milliron M, Tasian SK, Mackall CL. Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches. Cancer Immunol Immunother 2009; 58:1257-1264.
Xie XF, Ding Q, Hou JG, Chen G. Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer. Genet Mol Res 2015; 14:7548-7555.
Wang Y, Zheng N, Lu Z, Wu W, Wang L, Nakao A, et al. In vivo expansion of two distinct dendritic cells in mouse livers and its impact on liver immune regulation. Liver Transpl 2006; 12:1850-1861.
Burgdorf SK. Dendritic cell vaccination of patients with metastatic colorectal cancer. Dan Med Bull 2010; 57:B4171.
Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 2000; 191:423-434.
Jiang J, Xie D, Zhang W, Xiao G, Wen J. Fusion of Hsp70 to Mage-a1 enhances the potency of vaccine-specific immune responses. J Transl Med 2013; 11:300.
Goldszmid RS, Idoyaga J, Bravo AI, Steinman R, Mordoh J, Wainstok R. Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol 2003; 171:5940-5947.
Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, et al. STING-Dependent cytosolic DNA sensing promotes Radiation-Induced type i Interferon-Dependent antitumor immunity in immunogenic tumors. Immunity 2014; 41:843-852.