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.
Hou
Ming-Mo
MM
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chang
John Wen-Cheng
JW
Pang
See-Tong
ST
Chiang
Yang-Jen
YJ
Shen
Yung-Chi
YC
Liao
Shuen-Kuei
SK
Hsieh
Jia-Juan
JJ
Yeh
Kun-Yun
KY
Chang
Nai-Jen
NJ
Chuang
Cheng-Keng
CK
D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000951:Antigens, Neoplasm