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2002, Number 3

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Rev Inst Nal Enf Resp Mex 2002; 15 (3)

Alteration in the differentiation of immature human dendritic cells by lung adenocarcinomas.

Ávila MF, Sánchez TC, Rivas CA, Prado GH, López GJS

Language: Spanish
References: 41
Page: 135-142
PDF size: 94.91 Kb.


ABSTRACT

Introduction: Differentiation and maturation of dendritic cells (DCs) are characterized by changes in their phenotype and function. The DCs participation is crucial in the induction of an antitumor immune response. It has been reported that lung carcinomas elude the immune response using various strategies. Alterations in the DCs differentiation by lung adenocarcinoma, however, have not been described. Objective: To study alterations on the differentiation from monocytes to immature DCs (iDCs) due to soluble factors released by lung adenocarcinoma. Material and methods: CD14+ monocytes purified from peripheral blood mononuclear cells (MNC) were cultured with GM-CSF and IL-4 to induce differentiation to iDCs. Using the same procedure, soluble factors released from three different adenocarcinoma cell lines or from MNC (control) were added to the monocyte cultures. Changes in the percentage of positive cells and in the expression of CD14, HLA-DR, CD1a, CD32, CD40, CD11b, CD80, CD86 and CD83 molecules, measured as mean of fluorescence intensity (MF), were detected using flow cytometry. Proliferation rate was evaluated from co-cultures of iDCs and allogeneic T cells. Results: The soluble factors released by three lung adenocarcinoma lines tended in the iDCs to reduce the expression of CD1a, and to increase the percentage of cells and the expression of CD32. Only one cell line tended to increase the expression of HLA-DR. Inhibition of allogeneic T cells proliferation was detected when iDCs (previously stimulated with supernatants from tumor cells) were added to the co-cultures. Conclusion: Adenocarcinoma cell lines altered the differentiation process from monocytes to iDCs. Our results suggest that iDCs expressed a macrophage-like phenotype. This type of iDCs induced a strong inhibition on the proliferation rate of allogeneic T cells. DCs with these alterations might induce tolerance to the tumor antigens, blocking the induction of an efficient immune response against the tumor.


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