title: DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells.
abstract: Accumulating evidence suggests that most solid malignancies consist of heterogeneous tumor cells and that a relatively small subpopulation, which shares biological features with stem cells, survives through potentially lethal stresses such as chemotherapy and radiation treatment. Since the survival of this subpopulation of cancer stem cells (CSC) plays a critical role in recurrence, it must be eradicated in order to cure cancer. We previously reported that vaccination with CD133(+) murine melanoma cells exhibiting biological CSC features induced CSC-specific effector T cells. These were capable of eradicating CD133(+) tumor cells in vivo, thereby curing the parental tumor. In the current study, we indicated that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133(+) tumor cells. Vaccination with DDX3X primed specific T cells, resulting in protective and therapeutic antitumor immunity. The DDX3X-primed CD4(+) T cells produced CD133(+) tumor-specific IFNγ and IL-17 and mediated potent antitumor therapeutic efficacy. DDX3X is expressed in various human cancer cells, including lung, colon, and breast cancer cells. These results suggest that anti-DDX3X immunotherapy is a promising treatment option in efforts to eradicate CSC in the clinical setting.
authors: Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Course for Biological Functions and Medical Control, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
authors: Jun
authors: J
authors: Koshio
authors: Hiroshi
authors: H
authors: Kagamu
authors: Koichiro
authors: K
authors: Nozaki
authors: Yu
authors: Y
authors: Saida
authors: Tomohiro
authors: T
authors: Tanaka
authors: Satoshi
authors: S
authors: Shoji
authors: Natsue
authors: N
authors: Igarashi
authors: Satoru
authors: S
authors: Miura
authors: Masaaki
authors: M
authors: Okajima
authors: Satoshi
authors: S
authors: Watanabe
authors: Hirohisa
authors: H
authors: Yoshizawa
authors: Ichiei
authors: I
authors: Narita
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D053487:DEAD-box RNA Helicases / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000276:immunology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
references: Nature. 2006 Dec 7;444(7120):756-60
references: 17051156
references: J Exp Med. 2004 Apr 19;199(8):1133-42
references: 15096539
references: Cancer Res. 2005 May 15;65(10):4320-33
references: 15899824
references: J Immunol. 2005 Oct 15;175(8):5058-66
references: 16210609
references: Transplantation. 2011 Aug 15;92(3):359-65
references: 21709606
references: J Clin Oncol. 2008 Jun 10;26(17):2821-7
references: 18539960
references: Biochim Biophys Acta. 2011 Mar;1813(3):438-47
references: 21237216
references: Science. 1997 Oct 24;278(5338):675-80
references: 9381176
references: Blood. 2004 Jan 1;103(1):353-9
references: 14512314
references: Cancer Res. 2012 Feb 1;72(3):576-80
references: 22298594
references: Stem Cells. 2008 Dec;26(12):3008-17
references: 18802032
references: Blood. 2002 Apr 15;99(8):3027-32
references: 11929796
references: Semin Oncol. 2005 Dec;32(6 Suppl 9):S78-81
references: 16399438
references: Cell. 2008 May 16;133(4):704-15
references: 18485877
references: N Engl J Med. 2011 Dec 29;365(26):2497-506
references: 22150006
references: Science. 2011 Aug 26;333(6046):1157-60
references: 21798893
references: Nature. 2008 Apr 3;452(7187):650-3
references: 18385740
references: Cell. 2010 Apr 2;141(1):69-80
references: 20371346
references: J Immunol. 2001 Nov 15;167(10):5678-88
references: 11698440
references: Blood. 2008 May 1;111(9):4817-26
references: 18299450
references: Nature. 2007 Jan 4;445(7123):111-5
references: 17122771
references: Oncogene. 2008 Jun 26;27(28):3912-22
references: 18264132
references: Cancer Res. 2006 Jul 1;66(13):6579-88
references: 16818630
references: J Immunol. 2003 Dec 1;171(11):5828-36
references: 14634092
references: J Natl Cancer Inst. 2006 Dec 20;98(24):1755-7
references: 17179471
references: Clin Cancer Res. 2011 Apr 1;17(7):1895-905
references: 21325288
references: Nature. 2012 Aug 2;488(7409):106-10
references: 22820256
references: Cancer Immunol Immunother. 2011 Nov;60(11):1597-608
references: 21691723
references: J Immunol. 1998 Apr 1;160(7):3444-52
references: 9531305