Dendritic Cells and the Immunotherapy of Tumors

Overview

Dendritic cells (DC) constitute a heterogeneous leukocyte population. Their main function is to capture and processantigens (Ag) and present them to immunocompetent cells. Heterogeneity of DC is reflected at several levels. Myeloidand lymphoid lineage of the DC can be distinguished according to the precursor cell they originate from. Thefunctional differentiation is of the great importance. DC can induce either specific immune reaction or tolerance tocertain Ag. It depends upon the microenvironment where the processing of Ag takes place. Phenotypic and functionaldifferences between the subtypes of DC are being extensively investigated for the purpose of their use in theimmunotherapy of various diseases, tumors in particular. It appears that one of the causes of the specific anti-tumorimmunity failure is the insufficient function of DC in vivo in patients with malignant diseases. Recent technologyadvances has enabled to generate and cultivate DC in sufficient amounts in vitro from their precursors. Coculturingof DC with the tumor Ag in the presence of cytokine mixture leads to the efficient Ag presentation and to the generationof specific cytotoxic lymphocytes capable of killing tumor cells. Subsequent application of these tumor Ag pulsedDC 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 ofimmunotherapy 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 waysof their generation in vitro. We emphasize the use of DC in the clinical practice aimed at the immunotherapy oftumor diseases.

Key words:
dendritic cells, immunotherapy, tumor disease.