EXPRESSION OF CYTOKINE MESSENGER-RNA TRANSCRIPTS IN RENAL-CELL CARCINOMA

Renal cell carcinoma (RCC) is a solid tumour of the kidney and is the most common renal neoplasm. Despite the presence of tumour infiltratin g lymphocytes (TIL) in RCC, these tumours continue to progress in vivo suggesting a poor host immune response to the tumour, and the suppres sion of TIL effector function. Cytokines are key molecules that modula te the function of T cells. The possibility is investigated that the l ocal production of cytokines in RCC contributes to immunosuppression o f TIL. The expression of pro-inflammatory (IFN-gamma/IL-2) and immunos uppressive (IL-10/TGF-beta) cytokine mRNA transcripts was determined i n RCC, normal kidney and peripheral blood of RCC patients using a semi -quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with cytokine-specific primers. Following Southern blot hybridization of the PCR products with internal radiolabelled oligonucleotide probe s, cytokine transcript levels were measured by densitometry and expres sed relative to the glyceraldehyde-3-phosphate dehydrogenase densitome try score. With the exception of IL-10, there were no differences in e xpression of cytokine mRNA transcripts between the peripheral blood of patients and normal healthy individuals. It was found that `TGF-beta transcripts were well represented in normal kidney and RCC. In contras t, the expression of IFN-gamma transcripts, while low in the majority of samples, was significantly increased in RCC when compared to normal kidney (P = 0.05). The IL-2 and IL-10 transcripts showed a more varia ble expression in normal kidney and RCC, with no significant differenc es in expression between the sample groups. The data demonstrating pro -inflammatory and immunosuppressive cytokine expression in RCC do not support a prominent immunosuppressive cytokine profile in these tumour s.