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-alpha (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-alpha 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 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 E(2) did not increase the ability of immature DCs to stimulate T cell proliferation.

CONCLUSIONS

Patients with RCC have less potent anti-tumor immune responses.