title: Anti-CD40-induced inflammatory E-cadherin+ dendritic cells enhance T cell responses and antitumour immunity in murine Lewis lung carcinoma.
abstract: BACKGROUND
  Agonistic CD40 antibodies have been demonstrated to activate antigen-presenting cells (APCs) and enhance antitumour T cell responses, thereby providing a new therapeutic option in cancer immunotherapy. In agonistic CD40 antibody-mediated inflammatory responses, a novel subset of E-cadherin + dendritic cells (DCs) has been identified, and little is known about the role of these DCs in tumour immunity. This study investigated the effect of anti-CD40-mediated inflammatory E-cadherin + DCs in murine Lewis lung carcinoma (LLC).
  
  
  METHODS
  The phenotype and characteristics of anti-CD40-mediated inflammatory E-cadherin + DCs isolated from the anti-CD40 model were assessed in vitro. The antitumour activity of E-cadherin + DCs were evaluated in vivo by promoting the differentiation of effector CD4+ T cells, CEA-specific CD8+ T cells and CD103+ CD8+ T cells and assessing their resistance to tumour challenge, including variations in tumour volume and survival curves.
  
  
  RESULTS
  Here, we demonstrated that anti-CD40-mediated E-cadherin + inflammatory DCs accumulate in the lungs of Rag1 KO mice and were able to stimulate naïve CD4+ T cells to induce Th1 and Th17 cell differentiation and polarisation and to inhibit regulatory T cell and Th2 responses. Importantly, with the adoptive transfer of E-cadherin + DCs into the Lewis lung cancer model, the inflammatory DCs increased the Th1 and Th17 cell responses and reduced the Treg cell and Th2 responses. Interestingly, following the injection of inflammatory E-cadherin + DCs, the CD103+ CD8+ T cell and CEA-specific CD8+ T cell responses increased and exhibited potent antitumour immunity.
  
  
  CONCLUSIONS
  These findings indicate that anti-CD40-induced E-cadherin + DCs enhance T cell responses and antitumour activity in non-small cell lung cancer (NSCLC)-bearing mice and may be used to enhance the efficacy of DC-based peptide vaccines against NSCLC.
authors: Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan, 430023, Hubei, China. dmgy520@163.com.
authors: Yong
authors: Y
authors: Zhang
authors: Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan, 430023, Hubei, China. 673834043@qq.com.
authors: Xiaoyan
authors: X
authors: Hu
authors: Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan, 430023, Hubei, China. 597517574@qq.com.
authors: Yue
authors: Y
authors: Hu
authors: Hainan Cancer Hospital, Haikou, Hainan, China. tengkaitk@126.com.
authors: Kai
authors: K
authors: Teng
authors: Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan, 430023, Hubei, China. 951145296@qq.com.
authors: Kai
authors: K
authors: Zhang
authors: Department of oncology, Central Hospital of Wuhan, Wuhan, Hubei, China. 418039860@qq.com.
authors: Yamei
authors: Y
authors: Zheng
authors: Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan, 430023, Hubei, China. 15567050@qq.com.
authors: Xiaohua
authors: X
authors: Hong
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China. 543246702@qq.com.
authors: Kunwu
authors: K
authors: Yu
authors: Institute of Hydro Biololgy, Chinese Academy of Sciences, Analysis and Testing center, Wuhan, China. wangyan@ihb.ac.cn.
authors: Yan
authors: Y
authors: Wang
authors: Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan, 430023, Hubei, China. liulist2013@163.com.
authors: Li
authors: L
authors: Liu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D019013:CD40 Antigens / Q000037:antagonists & inhibitors*; D015820:Cadherins / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D007113:Immunity, Innate; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D019013:CD40 Antigens; D015820:Cadherins
references: Immunity. 2007 Apr;26(4):519-31
references: 17412618
references: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10811-6
references: 11526222
references: Cell Death Differ. 2008 Mar;15(3):504-14
references: 18049477
references: J Immunol. 2009 Jan 1;182(1):111-20
references: 19109141
references: Nat Immunol. 2009 Apr;10(4):394-402
references: 19252492
references: Nat Immunol. 2009 Nov;10(11):1178-84
references: 19783988
references: Cancer Immunol Immunother. 2011 Oct;60(10):1473-84
references: 21660450
references: Eur J Immunol. 2012 Oct;42(10):2535-43
references: 23042650
references: Nature. 2012 Nov 8;491(7423):254-8
references: 23034650
references: J Exp Clin Cancer Res. 2013;32:6
references: 23374147
references: Immunity. 2010 Apr 23;32(4):557-67
references: 20399121
references: Eur J Immunol. 2010 Dec;40(12):3478-88
references: 21108468
references: J Clin Invest. 2011 Jun;121(6):2254-63
references: 21537083
references: J Immunol. 2000 Jul 15;165(2):779-85
references: 10878351
references: Cancer Immunol Immunother. 2014 Sep;63(9):911-24
references: 24893855
references: Cancer Gene Ther. 2003 Jan;10(1):1-13
references: 12489023
references: Cancer Cell. 2003 Jul;4(1):31-9
references: 12892711
references: Cell. 1989 May 5;57(3):503-12
references: 2785856
references: Immunity. 1994 Sep;1(6):447-56
references: 7895156
references: Nature. 1996 Oct 31;383(6603):787-93
references: 8893001
references: J Exp Med. 1997 Aug 29;186(5):665-72
references: 9271582
references: Nature. 1998 Jun 4;393(6684):478-80
references: 9624004
references: J Exp Med. 1999 Feb 1;189(3):587-92
references: 9927520
references: Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1036-41
references: 9927689
references: Nat Rev Immunol. 2006 Apr;6(4):295-307
references: 16557261
references: Int Immunol. 2006 Jun;18(6):827-35
references: 16611649
references: J Exp Med. 2006 Oct 30;203(11):2441-50
references: 17043144
references: J Exp Med. 2006 Oct 30;203(11):2409-12
references: 17043147
references: Nat Med. 2007 Mar;13(3):354-60
references: 17334371
references: Infect Immun. 2007 May;75(5):2291-6
references: 17325050
references: Clin Cancer Res. 2013 Mar 1;19(5):1035-43
references: 23460534
references: Cancer Immunol Res. 2014 Jan;2(1):19-26
references: 24416732
references: Cancer Immunol Res. 2014 May;2(5):487-500
references: 24795361
references: J Exp Clin Cancer Res. 2014;33:35
references: 24761979
references: J Exp Med. 2007 Aug 6;204(8):1757-64
references: 17620361