Characterization of the response of dendritic cells and regulatory T cells to tumor antigens in patients with renal cell carcinoma

Background: This study characterized dendritic cells (DCs), regulatory T cells (Tregs) and the immune responses to tumor antigens in renal cell carcinoma (RCC) patients. Methods: Thirty patients with RCC and five healthy donors were studied. DCs were generated from the adherent cells among peripheral blood mononuclear cells (PBMCs), then cultured in medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 for 7 days. The phenotypes of the DCs and Tregs were analyzed by flow cytometry. A mixed lymphocyte reaction (MLR) was performed to assess the functioning of the DCs and Tregs. A cytotoxic assay was performed to measure the antigen presentation ability of the DCs from the RCC patients (RCC-DCs). These DCs were pretreated with TNF-á (TNF-DCs) or tumor lysate (TuLy-DCs) on the 3rd day of DC culture. Results: The RCC-DCs expressed significantly less CD40 (p = 0.03) and CD80 (p = 0.007) upon TNF-á cultivation than the DCs from healthy donors. The peripheral Tregs during stage I disease were significantly less (p = 0.032) than during stages II-IV. The RCC-DCs were as efficient as DCs from healthy donors (p = 0.83) when stimulating the proliferation of allogeneic T cells; however, these RCC-DCs were less efficient when stimulating autologous T cells than allogeneic T cells (p = 0.023). Tregs inhibited autologous T cell proliferation rather than allogeneic T cell proliferation in response to TuLy-DCs stimulation. Prostaglandin E2 did not increase the ability of immature DCs to stimulate T cell proliferation. Conclusions: Patients with RCC have less potent anti-tumor immune responses.