High expression of chemokine gene as a favorable prognostic factor in renal cell carcinoma

Purpose: The presence and potential role of chemokines in clinical tumors remain poorly understood. Chemokines are a large family of chemoattractant cytokines with several members that are also able to regulate angiogenesis. We hypothesized that chemokines may have an important role in regulating tumor growth in renal cell carcinoma (RCC). To begin to test this hypothesis chemokine gene expression and its influence on prognosis, cellular infiltration and angiogenesis in RCC were examined. Materials and Methods: A total of 51 patients with sporadic RCC were analyzed for the expression of the 7 chemokine genes interleukin-8, gamma-interferon inducible protein-10 (IP-10), monokine induced by gamma-interferon (MIG), macrophage chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated and activated normal T cells excreted and secreted (RANTES) using semiquantitative reverse transcriptase-polymerase chain reaction. Lymphocyte infiltration and rnicrovessel density were determined immunohistochemically by staining CD8(+) and CD34(+) cells, respectively. Results: The expression of IP-10, MIG, MIP-1beta and RANTES was significantly increased in tumor compared to normal kidney tissues. The expression of IP-10, MIG and MIP-1beta showed an inverse correlation with tumor size. Stages 1 to 3 tumors expressing high levels of IP-10, MIG, MIP-1beta and RANTES did not recur after curative surgery. Intratumor expression of IP-10, MIG and MIP-1beta showed a positive correlation with the degree of CD8(+) cell infiltrating in the tumor and an inverse correlation with microvessel density. Conclusions: These results suggest that IP-10, MIG and MIP-1beta are expressed at high levels in tumors that rarely recur after surgery. The antitumorigenic effect of IP-10, MIG and MIP-1beta may result from the recruitment of lymphocyte infiltration and/or inhibition of angiogenesis in RCC. The amplification of chemokine expression by immunotherapy or gene therapy may be a practical and effective strategy to promote tumor regression.