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) andthe immune responses to tumor antigens in renal cell carcinoma (RCC)patients.Methods: Thirty patients with RCC and five healthy donors were studied. DCs weregenerated from the adherent cells among peripheral blood mononuclear cells(PBMCs), then cultured in medium containing granulocyte-macrophagecolony-stimulating factor (GM-CSF) and IL-4 for 7 days. The phenotypes ofthe DCs and Tregs were analyzed by flow cytometry. A mixed lymphocytereaction (MLR) was performed to assess the functioning of the DCs andTregs. A cytotoxic assay was performed to measure the antigen presentationability of the DCs from the RCC patients (RCC-DCs). These DCs were pretreatedwith TNF-α (TNF-DCs) or tumor lysate (TuLy-DCs) on the 3rd day ofDC culture.Results: The RCC-DCs expressed significantly less CD40 (p = 0.03) and CD80 (p =0.007) upon TNF-α cultivation than the DCs from healthy donors. Theperipheral Tregs during stage I disease were significantly less (p = 0.032)than during stages II-IV. The RCC-DCs were as efficient as DCs fromhealthy donors (p = 0.83) when stimulating the proliferation of allogeneic Tcells; however, these RCC-DCs were less efficient when stimulating autologousT cells than allogeneic T cells (p = 0.023). Tregs inhibited autologous Tcell proliferation rather than allogeneic T cell proliferation in response toTuLy-DCs stimulation. Prostaglandin E2 did not increase the ability of immatureDCs to stimulate T cell proliferation.Conclusions: Patients with RCC have less potent anti-tumor immune responses.