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Dendritic cells and their use in the therapy of neoplastic diseases

Publication at Second Faculty of Medicine |
2000

Abstract

Dendritic cells (DC) constitute a heterogeneous leukocyte population. Their main function is to capture and process antigens (Ag) and present them to immunocompetent cells.

Heterogeneity of DC is reflected at several levels. Myeloid and lymphoid lineage of the DC can be distinguished according to the precursor cell they originate from.

The functional differentiation is of the great importance. DC can induce either specific immune reaction or tolerance to certain Ag.

It depends upon the microenvironment where the processing of Ag takes place. Phenotypic and functional differences between the subtypes of DC are being extensively investigated for the purpose of their use in the immunotherapy of various diseases, tumors in particular.

It appears that one of the causes of the specific anti-tumor immunity failure is the insufficient function of DC in vivo in patients with malignant diseases. Recent technology advances has enabled to generate and cultivate DC in sufficient amounts in vitro from their precursors.

Coculturing of DC with the tumor Ag in the presence of cytokine mixture leads to the efficient Ag presentation and to the generation of specific cytotoxic lymphocytes capable of killing tumor cells. Subsequent application of these tumor Ag pulsed DC to the laboratory animals, and to the patients in first clinical studies, can induce regression of malignant disease.

On the other side the ability of DC to induce tolerance to certain Ag is the subject of investigation in the field of immunotherapy of hypersensitivity states induced either by outer Ag (allergy) or inner Ag (autoimmune diseases). In this review we summarize source and ontogeny of DC, their morphology, phenotype, function and different ways of their generation in vitro.

We emphasize the use of DC in the clinical practice aimed at the immunotherapy of tumor diseases.