BERKELEY, CA (UroToday.com) - The infiltration of renal cell carcinoma (RCC) tumors by lymphocytes was initially thought to represent the host immune system attacking the tumor. Indeed therapies have been developed in the past that utilized these tumor infiltrating lymphocytes (TILs). Newer data suggest that these cells are not the immune system coming to the rescue but instead may be T regulatory cells that in fact may facilitate inhibition of antitumoral immunity. Lymphocytic infiltration of RCC tumors has been shown in this and other studies to be associated with an adverse prognosis. Here, the group from Mayo clinic sought to further characterize the phenotype of these infiltrating cells, through the use of specific antibodies (CD4, CD25, and FoxP3) that allow the identification of lymphocytes as specific members of the T cell regulatory family.

The authors stained tumors from 170 patients with clear cell RCC with antibodies against the above mentioned T cell specific antigens. Thirty-seven of the 170 were dead from RCC at the time of the analysis. The authors found that 25.3% of tumors had CD4+CD25+FoxP3+ infiltrating lymphocytes (natural T regulatory cells) but this was not associated with survival. They also found that 84.1% of tumors harbored CD4+CD25+FoxP3- lymphocytes. Patients with ≥ 10% of these cells had an increased risk of death from RCC (RR 2.6) even after adjusting for B7-H1 expression and the presence of lymphocytic infiltration as prognostic factors. This designation was lost, however, after adjusting for the Mayo SSIGN score. The presence of ≥ 10% CD4+CD25+FoxP3- cells was associated with increased tumor size, TNM stage, and the presence of coaguative necrosis. The 3 year cancer specific survival for those patients with <10% was 86.5%, as compared to 65.4% in patients with ≥ 10%.

The authors conclude that this subset of T cells (CD4+CD25+FoxP3-) represent a unique group of T cells infiltrating the tumor and are associated with adverse outcomes when present.

Siddiqui SA, Frigola X, Bonne-Annee S, Mercader M, Kuntz SM, Krambeck AE, Sengupta S, Dong H, Cheville JC, Lohse CM, Krco CJ, Webster WS, Leibovich BC, Blute ML, Knutson KL, Kwon ED

Clin Cancer Res. 13(7): 2075-2081, April 2007
doi: 10.1158/1078-0432.CCR-06-2139

UroToday.com Renal Cancer Section

Written by Christopher G. Wood, MD, a Contributing Editor with UroToday.

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