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Questionable Relevance of T Lymphocytes in Renal Cell Carcinoma¹

Brant A. Inman^*, Xavier Frigola, Kimberley J. Harris, Susan M. Kuntz, Christine M. Lohse, Bradley C. Leibovich^* and Eugene D. Kwon^2,*,

^* Department of Urology, Department of Immunology, and Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905

Adoptive T cell immunotherapy has moved briskly into clinical trials prompted by several small studies suggesting abundant accumulation of T cells within renal cell carcinoma (RCC). In this study, we re-examined levels of T cells within RCC tumors and correlated levels of these cells with pathologic features and outcome associated with this form of cancer. Tissues from 248 consecutive clear cell RCC tumors obtained from 2000 to 2003 were stained and quantified for total CD3⁺ and T cells per mm². Wilcoxon rank sum and Kruskal-Wallis tests were used to evaluate associations between T cell amounts and prognostic factors (age, gender, tumor size, stage, grade, tumor necrosis). Cox models were used to assess associations with RCC-specific death. Median numbers of total CD3⁺ and T cells were 281/mm² (interquartile range (IQR): 149–536) and 2.6/mm² (IQR: 1.3–4.6), respectively. The median percentage of CD3⁺ T cells that were T cells was 1.0% (IQR: 0.4–1.9). This low percentage of intratumoral T cells was diluted even further with rising CD3⁺ T cell infiltration. Percentages of T cells were not associated with even one single clinicopathologic feature examined. Median follow-up for this study was 3.1 years (48 patients died of RCC) and Cox analysis failed to demonstrate that T cells (hazard ratio = 1.02, p = 0.25) were predictive of RCC-specific death. T cells are rare and not recruited nor expanded within RCC tumors. Percentages of T cells fail to correlate with any prognostic features of RCC nor specific death. As such, the role of T cells in RCC immunobiology remains questionable.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by gifts from The Richard M. Schulze Family Foundation and The Commonwealth Foundation for Cancer Research. Donations were also provided by the Helen and Martin Kimmel Foundation.

² Address correspondence and reprint requests to Dr. Eugene D. Kwon, Department of Urology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905. E-mail address: kwon.eugene{at}mayo.edu

³ Abbreviations used in this paper: RCC, renal cell carcinoma; ccRCC, clear cell RCC; CI, confidence interval; IQR, interquartile range; IHC, immunohistochemistry.