SDF1β expression in renal cell carcinoma correlates with grading and infiltration by CD8+ T-cells.
2011
For several tumor entities, a significant correlation between the chemokine stromal cell-derived factor 1 (SDF1) and its receptor C-X-C chemokine receptor type 4 (CXCR4), metastasis and tumor proliferation, as well as prognosis, has been described. In this study, a series of 105 renal cell carcinoma patients were analyzed in terms of expression of SDF1α and SDF1β and infiltration by CD4 + and CD8 + T-cells and the data correlated with TNM category, grading and survival. While the splice variant SDF1α had no impact on tumor grading, T-cell invasion or overall survival, expression of SDF1β showed a significant correlation with tumor grading and also suggested a correlation with metastasis, as well as CD8 + T-cell invasion. These results indicate a potential T-cell-mediated antitumor response induced by SDF1β up-regulation. Therefore targeting the SDF1β-CXCR4 signaling pathway may be a promising means for new therapeutic strategies in advanced tumor stages. Renal cell carcinoma (RCC) is the sixth leading cause of cancer-related deaths in the Western world. RCC makes up 2-3% of all newly diagnosed malignancies in adults and 85% of all kidney tumors (1). The age-adjusted incidence of RCC in Western nations is 5 and 12/100,000 in women and men, respectively (2), with a peak incidence in the 6th decade. Early diagnosed stages can be cured by nephrectomy. However, approximately one-third of the patients experience relapse and progression with metastatic disease. About 30-50% of patients already have metastatic disease at presentation. The preferential sites of metastasis are the regional lymph nodes, the lung, the liver and the bones. Survival strongly depends on the tumor stage at presentation. The 5-year survival rate is approximately 50%, whereas the median survival in cases of metastasis is less than one year (3-5). The current standard treatment for metastasized RCC consists of interferon-α (IFN-α) and
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