EVALUATING THE EFFECT OF MELPHALAN-INDUCED DAMAGED DNA ON EXPRESSION OF MATURITY MARKERS AND POLARIZATION OF IMMUNE PHENOTYPES OF DENDRITIC CELLS

Morshedi, A and Delirezh, N and Parvin, P and Mokarizadeh, A (2012) EVALUATING THE EFFECT OF MELPHALAN-INDUCED DAMAGED DNA ON EXPRESSION OF MATURITY MARKERS AND POLARIZATION OF IMMUNE PHENOTYPES OF DENDRITIC CELLS. URMIA MED J, 23 (3). pp. 304-314.

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Abstract

Dendritic cells are the most potent antigen presenting cells in induction or polarization of T-dependent immune responses. In cancerous patients, suppressive or detoured immune responses regard to tumor cells, prevent appropriate functions of dendritic cells. Nowadays, in vitro production, expansion and maturation of dendritic cells in presence of safe maturation factors which polarize TH1 responses in donors, is the base of many cancer immunotherapy studies. The aim of this study was to evaluate the effect of melphalan-induced damaged DNA on dendritic cell maturation, phenotypes and its induced immune responses in T helper cells related to improvement or aggravation of the disease. Material & Methods: In this study, we analyzed the effect of MCF-7 derived damaged DNA (Induced by melphalan alkylating agent) in addition to standard maturation factors (TNF-α and MCM) on maturity characters of dendritic cells consisting of morphology, phenotype, phagocytosis, MLR, and cytokine secretion compared with the control group. Results: The data showed that the combination of damaged DNA with standard maturation factors in treatment of dendritic cells result to an increased expression in CD83 (the marker of matured DC) and a decreased levels of phagocytosis. Besides, damaged DNA polarized immune responses to DC1 phenotype triggering TH1 responses. Conclusion: Results demonstrate the efficiency of damaged DNA in induction of mature dendritic cells and their appropriate immune responses against MCF-7 cell line.

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