Abstract
Dendritic cells (DCs) are one of the most powerful antigen-presenting cells and play a crucial role in bridging between innate and acquired immunity. Cancer antigens or the long peptides are engulfed by DCs, digested into helper and killer epitope peptides, transported to the cell surface, and presented to CD4+ and CD8+ T cells through major histocompatibility complex (MHC) class II and MHC class I to induce effector T helper cells and cytotoxic killer T cells, respectively. In addition, DCs produce type 1 cytokines such as interleukin (IL)-12 and interferon (IFN)-α/-β to facilitate differentiation of naïve T cells into effector T cells and activation of memory T cells. Therefore, proper regulation of DC function is essential for induction and augmentation of anti-tumor immunity in cancer patients. Generally, DCs are immediately activated by various maturation signals including Toll-like-receptor (TLR) ligands, type 1 cytokines, and CD40/40L interaction. On the other hand, IL-6 produced in tumor microenvironments caused dysfunction of DCs through reduction of MHC class II expression and IL-12 production. It has recently been reported that zinc transporter-mediated intracellular zinc levels and neuropeptide signaling through the receptors are involved in the regulation of the antigen-presenting function of DCs in type 1 immune responses, including TLR-mediated inflammatory response. In this chapter, we report on regulation of the antigen-presenting function and the potential benefit of DC-mediated cancer immunotherapy.
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Kamon H, Kawabe T, Kitamura H et al (2006) TRIF-GEFH1-RhoB cascade regulates surface expression of MHC class II in dendritic cells that is critical for CD4+ T cell activation. EMBO J 25(17):4108–4119
Kitamura H, Iwakabe K, Yahata T et al (1999) The natural killer T (NKT) cell ligand α-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 189(7):1121–1128
Kitamura H, Kamon H, Sawa SH et al (2005) IL-6-STAT3 controls intracellular MHC class II αβ-dimer level through Cathepsin S activity in dendritic cells. Immunity 23:491–502
Kitamura H, Morikawa H, Kamon H et al (2006) Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol 7(9):971–977
Kitamura H, Kobayashi M, Wakita D et al (2012) Neuropeptide signaling activates dendritic cell-mediated type 1 immune responses through neurokinin-2 receptor. J Immunol 188(9):4200–4208. doi:10.4049/jimmunol.110252
Narita Y, Kitamura H, Wakita D et al (2013) The key role of IL-6-arginase cascade for inducing dendritic cell-dependent CD4+ T cell dysfunction in tumor-bearing mice. J Immunol 190(2):812–820. doi:10.4049/jimmunol.1103797
Ohtake J, Ohkuri T, Togashi Y et al (2014) Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine. Immunol Lett. 61(1):20–30. doi:http://dx.doi.org/10.1016/j.imlet.2014.04.010
Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancr 12(4):265–277. doi:10.1038/nrc3258
Palucka K, Ueno H, Banchereau J (2011) Recent developments in cancer vaccines. J Immunol 186:1325–1331. doi:10.4049/jimmunol.0902539
Park SJ, Nakagawa T, Kitamura H et al (2004) IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J Immunol 173(6):3844–3854
Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137(5):1142–1162
Steinman RM, Hemmi H (2006) Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol 311:17–58
Takahashi N, Ohkuri T, Homma S et al (2012) First clinical trial of cancer vaccine therapy with artificially synthesized helper/killer-hybrid epitope long peptide of MAGE-A4 cancer antigen. Cancer Sci 130(1):150–153. doi:10.1111/j.1349-7006.2011.02106.x
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Kitamura, H. et al. (2015). Regulation of Antigen Presentation by Dendritic Cells and Its Application to Cancer Immunotherapy. In: Seya, T., Matsumoto, M., Udaka, K., Sato, N. (eds) Inflammation and Immunity in Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55327-4_15
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DOI: https://doi.org/10.1007/978-4-431-55327-4_15
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55326-7
Online ISBN: 978-4-431-55327-4
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