Questionable relevance of γδ T lymphocytes in renal cell carcinoma

Adoptive γδ T cell immunotherapy has moved briskly into clinical trials prompted by several small studies suggesting abundant accumulation of γδ T cells within renal cell carcinoma (RCC). In this study, we re-examined levels of γδ 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 γδ 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 γδ 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 γδ T cells was 1.0% (IQR: 0.4 -1.9). This low percentage of intratumoral γδ T cells was diluted even further with rising CD3⁺ T cell infiltration. Percentages of γδ 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 γδ T cells (hazard ratio = 1.02, p = 0.25) were predictive of RCC-specific death. γδT cells are rare and not recruited nor expanded within RCC tumors. Percentages of γδT cells fail to correlate with any prognostic features of RCC nor specific death. As such, the role of γδ T cells in RCC immunobiology remains questionable.