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2015 | 87 | 2 | 71-82
Tytuł artykułu

Immunomodelling Characteristics of Mature Dendritic Cells Stimulated by Colon Cancer Cells Lysates

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Application of cells with high TAA (tumor associated antigen) presentation potential seems to be crucial in neoplasia immunotherapy. Such feature is distributed in dendritic cells, which present peptides from processed TAA - MHC molecules complex to the T cells of a host. The aim of the study was to assess the influence of colon neoplasia tissue lysate on functioning of generated autologous DC’s in the field of autologous CD4+ lymphocytes immunological response towards Th1/Th2 under in vitro environment together with comparison and assessment of DCs’ immunosuppressive properties acquired from patients with colon cancer. Material and methods. The population of this study consisted of 16 healthy- controls, 36colon cancer patients. Blood samples were collected 24h before planned surgery and preventive antibiotic therapy. Neoplastic tissue sample, was digested for cell lysates preparation. DC’s generation from PBMC was carried out in standard conditionsand medium enriched with rhGM-CSF and rhIL-4. Mature DC`s and cocultured autologous CD4 lymphocytes immunophenotype assessment was analyzed with flow cytometer. Intracellular and culture medium cytokines concentration was analyzed with ELISA and FACS method. Results. DC`s generated from colon cancer patients stimulated with lysates presented greater maturity, lower expression of CD206 antigen, significantly higher expression of HLA-DR, CD208 and CD209 and high intracellular expression of IL-12, compared to non-stimulated cells. Conclusions. The neoplastic tissue in vivo produces a number of substances having an unfavorable effect on immune system, our results suggests using lysates as good dendritic cells stimulators that possibly could have application in colon cancer immunotherapy
Słowa kluczowe
Wydawca
Rocznik
Tom
87
Numer
2
Strony
71-82
Opis fizyczny
Daty
wydano
2015-02-01
otrzymano
2015-01-31
online
2015-07-03
Twórcy
  • Department of Human Anatomy, Medical University in Lublin1 Kierownik: prof. dr hab. R. Maciejewski , radejs@wp.pl
  • Department of Clinical Immunology, Medical University in Lublin2 Kierownik: prof. dr hab. J. Roliński PhD student
  • Department of Surgical Oncology, Medical University in Lublin
autor
  • Department of General and Gastroenterological Surgery and Surgical Oncology of the Alimentary Tract, Medical University in Lublin
  • Department of General and Gastroenterological Surgery and Surgical Oncology of the Alimentary Tract, Medical University in Lublin
  • Department of General and Transplant Surgery and Nutritional Treatment, Medical University in Lublin
  • Department of General and Oncological Surgery, District Specialist Hospital in Lublin
  • Department of General and Gastroenterological Surgery and Surgical Oncology of the Alimentary Tract, Medical University in Lublin
  • Department of Human Anatomy, Medical University in Lublin1 Kierownik: prof. dr hab. R. Maciejewski
Bibliografia
  • 1. Scurr M, Ladell K, Besneux M et al.: Highly prevalent colorectal cancer-infiltrating LAPţFoxp3- T cells exhibit more potent immunosuppressive activity than Foxp3ţ regulatory T cells. MucosalImmunology 2014; 7(2): 428-39.
  • 2. Madhav D. Sharma, De-Yan Hou, Yanjun Liu et al.: Indoleamine 2,3-dioxygenase controls conversion of Foxp3_ Tregs to TH17-like cells in tumordraining lymph nodes. Blood 2009; 113(24): 6102-11.
  • 3. Liufu Deng, Haizeng Zhang, Yan Luan et al.: Accumulation of Foxp3+ T Regulatory Cells in Draining Lymph Nodes Correlates with Disease Progression and Immune Suppression in Colorectal Cancer Patients. Clin Cancer Res 2010; 16: 4105-4112. Published OnlineFirst August 3, 2010.
  • 4. Kim M, Grimmig T, Grimm M et al.: Expression of Foxp3 in Colorectal Cancer but Not in Treg Cells Correlates with Disease Progression in Patients with Colorectal Cancer. PLOS ONE, 2013; 8(1): 1-10.
  • 5. Itoh T, Ueda Y, Kawashima I et al.: Immunotherapy of solid cancer using dendritic cells pulsed with theHLA-A24-restricted peptide of carcinoembryonic antigen. Cancer ImmunolImmunother 2002; 51(2): 99-106. Epub 2002 Jan 30. 3
  • 6. Loddenkemper C, Schernus M, Noutsias M et al.: In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer. Transl Med 2006, 13(4): 52-54.
  • 7. Banerjee DK , Dhodapkar MV, Matayeva E et al.: Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients. Blood 2006,15;108(8):2655-61. Epub 2006 Jun 8. 8
  • 8. Rains N, Cannan RJ, Chen W, Stubbs RS: Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer. Hepatogastroenterology 2001; 48(38): 347-51.
  • 9. Fong L, Hou Y, Rivas A et al.: EnglemanEG. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 2001,17;98(15):8809-14. Epub 2001 Jun 26. 2
  • 10. Matsumoto A, Haraguchi K, Takahashi T et al.: Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells. Inter J Urology 2007; 14: 277-83.
  • 11. Holtl L, Zelle-Rieser C, Gander H et al.: Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 2002; 8: 3369-76.
  • 12. Arroyo JC, Gabilondo F, Llorente L et al.: Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines. J Clin Immunol 2004; 24: 86-96.
  • 13. Chen L, Meng D, Zhao L et al.: Selective colorectal cancer cell lysates enhance the immune function of mature dendritic cells in vitro. Mol Med Rep 2014; Nov 12.
  • 14. Nonaka M, Ma BY, Murai R et al.: Glycosylation- Dependent Interactions of C-Type Lectin DCSIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells. J Immunol 2008; 180: 3347-56.
  • 15. Kichler-Lakomy C, Budinsky AC , Wolfram R et al.: Deficiences in phenotype expression and function of dentritic cells from patients with early breast cancer. Eur J Med Res 2006, 11: 7-12.
  • 16. Remmel E, Terracciano L, Noppen C et al.: Modulation of dendritic cell phenotype and mobility by tumor cells in vitro. Hum Immunol 2001; 62: 39-49.
  • 17. Hunyadi J, András C, Szabó I et al.: Autologous Dendritic Cell Based Adoptive Immunotherapy of Patients with Colorectal Cancer-A Phase I-II Study. Pathol Oncol Res 2013; 28.
  • 18. Ghanekar SA, Bhatia S, Ruitenberg JJ et al.: Phenotype and in vitro function of mature MDDC generated from cryopreserved PBMC of cancer patients are equivalent to those from healthy donors. J Immune Based Ther Vaccines 2007; 5: 7.
  • 19. Pellegatta S, Eoli M, Frigerio S et al.: The natural killer cell response and tumor debulking are associated with prolonged survival in recurrent glioblastoma patients receiving dendritic cells loaded with autologous tumor lysates. Oncoimmunology 2013; 1: 2(3).
  • 20. Galea-Lauri J, Wells JW, Darling D et al.: Strategies for antigen choice and priming of dendritic cells influence the polarization and efficacy of antitumor T-cell responses in dendritic cell-based cancer vaccination. Cancer Immunol Immunother 2004; 53: 963-77.
  • 21. Lesterhuis WJ, de Vries IJ, Schuurhuis DH et al.: Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests. Ann Oncol 2006; 17: 974-80.
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.-psjd-doi-10_1515_pjs-2015-0022
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