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

Chang Gung Med J. 2010 Jan-Feb;33(1):25-35.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigen Presentation
  • Antigens, Neoplasm / immunology*
  • Carcinoma, Renal Cell / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Kidney Neoplasms / immunology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antigens, Neoplasm