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
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.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.