Abstract
Recent cancer biology research has suggested that cancer stem cells/cancer-initiating cells (CSCs/CICs) exist in most tumor tissues. They show self-renewal, differentiation, and, most importantly, tumorigenic potential. Thus, the possibility of regulating CSCs/CICs immunologically is highly intriguing. Our recent studies suggest that CSC/CIC-specific antigens, designated ‘cancer testis stem cell antigens’, are generally highly immunogenic, and should be useful for immunotherapeutic as well as prophylactic treatment of cancers. Since the clonal expansion of peripheral T lymphocytes is limited in vivo, immunological targeting of CSCs/CICs by cytotoxic T lymphocyte is thought to be the most rational and efficient approach for the treatment of and prophylaxis against cancers. In particular, cancer testis stem cell antigens might act as primordial tumor antigens in the basic immune surveillance mechanisms against tumors.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cho JM, Sato N, Yagihashi A, Konno A, Hara I, Konn S, Torigoe T, Qi W, Takashima T, Takahashi N et al (1991) Natural killer target molecules associated with the transformation of the oncogene-transfected fibroblast. Cancer Res 51(16):4250–4256
Hirohashi Y, Torigoe T, Maeda A, Nabeta Y, Kamiguchi K, Sato T, Yoda J, Ikeda H, Hirata K, Yamanaka N, Sato N (2002) An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin. Clin Cancer Res 8(6):1731–1739
Hirohashi Y, Torigoe T, Inoda S, Kobayashi J, Nakatsugawa M, Mori T, Hara I, Sato N (2009a) The functioning antigens; beyond just as the immunologic targets. Cancer Sci 100:798–806
Hirohashi Y, Torigoe T, Hirai I, Tamura Y, Nakatsugawa M, Inoue Y, Kanaseki T, Kamiguchi K, Ikeda H, Sasaki A, Yamanaka N, Sato N (2009b) Establishment of shared antigen reactive cytotoxic T lymphocytes using co-stimulatory molecule introduced autologous cancer cells. Exp Mol Pathol 88:128–132
Hirohashi Y, Torigoe T, Inoda S, Takahashi A, Morita R, Nishizawa S, Tamura Y, Suzuki H, Yoyota M, Sato N (2010) Immune response against tumor antigens expressed on human cancer stem-like cells/tumor-initiating cells. Immunotherapy 2:201–211
Hirohashi Y, Torigoe T, Inoda S, Morita R, Kochin V, Sato N (2012) Cytotoxic T lymphocytes: sniping cancer stem cells. Oncoimmunology 1:123–125
Honma I, Kitamura H, Torigoe A, Takahashi T, Tanaka T, Sato E, Hirohashi Y, Masumori N, Tsukamoto T, Sato N (2009a) Phase I clinical study of anti-apoptosis protein survivin-derived peptide vaccination for patients with advanced or recurrent urothelial cancer. Cancer Immunol Immunother 58:1801–1807
Honma I, Torigoe T, Hirohashi Y, Kitamura H, Sato E, Masumori N, Tamura Y, Tsukamoto T, Sato N (2009b) Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer. J Transl Med 7:103–110
Idenoue S, Hirohashi Y, Torigoe T, Sato Y, Tamura Y, Hariu H, Yamamoto M, Kurotaki T, Tsuruma T, Asanuma H, Kanaseki T, Ikeda H, Kashiwagi K, Okazaki M, Sasaki K, Sato T, Ohmura T, Hata F, Yamaguchi K, Hirata K, Sato N (2005) A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins. Clin Cancer Res 11(4):1474–1478
Inoda S, Hirohashi Y, Torigoe T, Nakatsugawa M, Kiriyama K, Harada K, Takasu H, Tamura Y, Kamiguchi K, Asanuma H, Tsuruma T, Terui T, Ishitani K, Ohmura T, Hasegawa T, Hirata K, Sato N (2009) Cep55/c10orf3, a tumor antigen derived from a centrosome residing protein in breast carcinoma. J Immunother 32:474–485
Inoda S, Hirohashi Y, Torigoe T, Takahashi A, Morita R, Nakatsugawa M, Nishizawa S, Tamura Y, Tsuruma T, Terui T, Ishitani K, Hirata K, Sato N (2011a) Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells. Am J Pathol 178:1805–1813
Inoda S, Morita R, Hirohashi Y, Torigoe T, Asanuma H, Nakazawa E, Nakatsugawa M, Tamura Y, Kamiguchi K, Tsuruma T, Terui T, Ishitani K, Hashino S, Wang Q, Greene MI, Hasegawa T, Hirata K, Asaka M, Sato N (2011b) The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma. Exp Mol Pathol 90:55–60
Kameshima H, Tsuruma T, Torigoe T, Takahashi A, Hirohashi Y, Tamura Y, Tsukahara T, Ichimiya S, Kanaseki T, Iwayama Y, Sato N, Hirata K (2011) Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients. Cancer Sci 102:1181–1187
Kameshima H, Tsuruma T, Kutomi G, Shima H, Iwayama Y, Kimura Y, Imamura M, Torigoe T, Takahashi A, Hirohashi Y, Tamura Y, Tsukahara T, Kanaseki T, Sato N, Hirata K (2013) Immunotherapeutic benefit of α-interferon (IFNα) in survivin2B-derived peptide vaccination for advanced pancreatic cancer patients. Cancer Sci 104:124–129
Kanki K1, Torigoe T, Hirai I, Sahara H, Kamiguchi K, Tamura Y, Yagihashi A, Sato N (2000) Molecular cloning of rat NK target structure–the possibility of CD44 involvement in NK cell-mediated lysis. Microbiol Immunol 44(12):1051–1061
Kano M, Tsukahara T, Emori M, Murase M, Torigoe T, Kawaguchi S, Wada T, Yamashita T, Sato N (2011) Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma. Cancer Sci 102:1443–1447
Kawaguchi S, Tsukahara T, Ida K, Kimura S, Murase M, Kano M, Emori M, Nagoya S, Kaya M, Torigoe T, Ueda E, Takahashi A, Ishii T, Tatezaki S, Toguchida J, Tsuchiya H, Osanai T, Sugita T, Sugiura H, Ieguchi M, Ihara K, Hamada K, Kakizaki H, Morii T, Yasuda T, Tanizawa T, Ogose A, Yabe H, Yamashita T, Sato N, Wada T (2012) SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group. Cancer Sci 103:1625–1630
Kitamura H, Torigoe T, Hirohashi Y, Asanima H, Inoue R, Nishida S, Tanaka T, Masumori M, Sato N, Tsukamoto T (2013a) Nuclear, but not cytoplasmic, localization of survivin as a negative prognostic factor for survival in upper urinary tract urothelial carcinoma. Virchows Arch 462:101–107
Kitamura H, Torigoe T, Hirohashi Y, Asanuma H, Inoue R, Nishida S, Tanaka T, Fukuta F, Masumori N, Sato N, Tsukamoto T (2013b) Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract. Mod Pathol 26:117–124
Kobayashi J, Torigoe T, Hirohashi Y, Idenoue S, Miyazaki A, Yamaguchi A, Hiratsuka H, Sato N (2009) Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant surviving-2B in oral cancer patients. J Transl Med 7:1–11
Konno A, Sato N, Yagihashi A, Torigoe T, Cho JM, Torimoto K, Hara I, Wada Y, Okubo M, Takahashi N et al (1989) Heat- or stress-inducible transformation-associated cell surface antigen on the activated H-ras oncogene-transfected rat fibroblast. Cancer Res 49(23):6578–6582
Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N (2013) ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis. PLoS One 8(6):e65158
Michifuri Y, Hirohashi Y, Torigoe T, Miyazaki A, Kobayashi J, Sasaki T, Fujino J, Asanuma H, Tamura Y, Nakamori K, Hasegawa T, Hiratsuka H, Sato N (2012) High expression of ALDH1 and SOX2 diffuse staining pattern of oral squamous cell carcinomas correlates to lymph node metastasis. Pathol Int 62:684–689
Michifuri Y, Hirohashi Y, Torigoe T, Miyazaki A, Fujino J, Tamura Y, Tsukahara T, Kanaseki T, Kobayashi J, Sasaki T, Takahashi A, Nakamori K, Yamaguchi A, Hiratsuka H, Sato N (2013) Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer stem-like cells and is related to their growth through activation of MAP kinase signal. Biochem Biophys Res Commun 439:96–102. doi:10.1016/j.bbrc.2013.08.021
Miyazaki A, Kobayashi J, Torigoe T, Hirohashi Y, Yamamoto T, Yamaguchi A, Asanuma H, Takahashi A, Michifuri Y, Nakamori K, Nagai I, Sato N, Hiratsuka H (2011) Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer. Cancer Sci 102:324–329
Mori T, Nishizawa S, Hirohashi Y, Torigoe T, Tamura Y, Takahashi A, Kochin V, Fujii R, Toru K, Greene MI, Hara I, Sato N (2012) Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population. Exp Mol Pathol 92:27–32
Morita R, Hirohashi Y, Suzuki H, Takahashi A, Tamura Y, Kanaseki T, Asanuma H, Inoda S, Kondo T, Hashino S, Hasegawa T, Tokino T, Toyota M, Asaka M, Torigoe T, Sato N (2013) DNA methyltransferase 1 is essential for initiation of the colon cancers. Exp Mol Pathol 94:322–327
Murase M, Kano M, Tsukahara T, Takahashi A, Torigoe T, Kawaguchi S, Kimura S, Wada T, Uchihashi Y, Kondo T, Yamashita T, Sato N (2009) Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas. Brit J Cancer 101:1425–1432
Nakatsugawa M, Takahashi A, Hirohashi Y, Torigoe T, Inoda S, Asanuma H, Tamura Y, Hasegawa T, Takahashi H, Sato N (2011) SOX2 is expressed in stem-like cells of human lung adenocarcinoma and augments the tumor-initiating potential. Lab Invest 91:1796–1804
Nishida S, Hirohashi Y, Torigoe T, Kitamura H, Takahashi A, Masumori N, Tsukamoto T, Sato N (2012) Gene expression profiles of prostate cancer stem cells isolated by aldehyde dehydrogenase activity assay. J Urol 88:294–299
Nishida S, Hirohashi Y, Torigoe T, Inoue R, Kitamura H, Tanaka T, Takahashi A, Asanima H, Masumori N, Tsukamoto T, Sato N (2013) Prostate cancer stem-like cells/cancer-initiating cells have an autocrine system of hepatocyte growth factor. Cancer Sci 104:431–436
Nishizawa S, Mori T, Hirohashi Y, Torigoe T, Tamura Y, Kamiguchi K, Takahashi A, Kanaseki T, Nakazawa E, Asanuma H, Sokolovskaya A, Morita R, Yamada R, Fujii R, Kondo T, Hasegawa T, Hara I, Sato N (2012) Heat shock protein 40 family, DNAJB8 is expressed in renal cancer stem-like cell, controls the tumor-initiating ability and can be a potent target of immunotherapy. Cancer Res 72:2844–2854
Sato N, Hirohashi Y, Tsukahara T, Kikuchi T, Sahara H, Kamiguchi K, Ichimiya S, Tamura H, Torigoe T (2009) Molecular pathologic approaches to human tumor immunology. Pathol Int 59:205–217
Takahashi A, Torigoe T, Tamura Y, Kanaseki T, Tsukahara T, Sasaki Y, Kameshima H, Tsuruma T, Hirata K, Tokino T, Hirohashi Y, Sato N (2012) Heat shock enhances the expression of cytotoxic granule proteins and augments the activities of tumor-associated antigen-specific cytotoxic T lymphocytes. Cell Stress Chaperones 17:757–763
Torigoe T, Tamura Y, Sato N (2009) Heat shock proteins and immunity: application of hyperthermia for immunomodulation. Int J Hyperthermia 25:610–616
Torigoe T, Hirohashi Y, Yasuda K, Sato N (2013) Constitutive expression and activation of stress response genes in cancer stem-like cells/tumour initiating cells: potent targets for cancer stem cell therapy. Int J Hyperthermia 29:436–441. doi:10.3109/02656736.2013.814809
Tsukahara T, Kawaguchi S, Torigoe T, Takahashi A, Murase M, Kano M, Wada T, Kaya M, Nagoya S, Yamashita T, Sato N (2009) HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor. J Transl Med 7:44–51
Tsuruma T, Iwayama Y, Ohmura T, Katsuramaki T, Hata F, Furuhata T, Yamaguchi K, Kimura Y, Torigoe T, Toyota N, Yagihashi A, Hirohashi Y, Asanuma H, Shimozawa K, Okazaki M, Mizushima Y, Nomura N, Sato N, Hirata K (2008) Clinical and immunological evaluation of anti-apoptosis protein, surviving-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer. J Transl Med 6:24–35
Yagihashi A, Sato N, Torigoe T, Okubo M, Konno A, Takahashi N, Yamashita T, Fujinaga K, Kuzumaki N, Kikuchi K (1988) Identification of the transformation-associated cell surface antigen expressed on the rat fetus-derived fibroblast. Cancer Res 48(10):2798–2804
Yamada R, Takahashi A, Torigoe T, Morita R, Tamura Y, Tsukahara T, Kanaseki T, Kubo T, Watarai K, Kondo T, Hirohashi Y, Sato N (2013) Preferential expression of cancer/testis genes in cancer stem-like cells: proposal of a novel sub-category, cancer/testis/stem gene. Tissue Antigens 81:428–434
Yasuda K, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, Kochin V, Asanuma H, Hasegawa T, Saito T, Hirohashi Y, Sato T (2013) Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population. PLoS One 8(8):e68187. doi:10.1371/journal.pone.0068187
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Japan
About this chapter
Cite this chapter
Sato, N. et al. (2015). Immunological Regulation of Human Cancer Stem Cells/Cancer-Initiating Cells. 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_19
Download citation
DOI: https://doi.org/10.1007/978-4-431-55327-4_19
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55326-7
Online ISBN: 978-4-431-55327-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)