INTERACTION OF TUMOR AND IMMUNE-SYSTEM IN RENAL CELL CARCINOMAS AND MELANOMAS - CYTOKINE GENE-TRANSCRIPTION IN TUMORS IN SURGICAL RESECTION

Tumor infiltrating lymphocytes (TIL) of many tumors express surface ac tivation markers. An antigen driven stimulation of T-lymphocytes is ex pected to induce not only cell membrane activation molecules but also a unique pattern of cytokine gene transcripts. These cytokines are rel evant modulators and potent effectors of immune responses, and therefo re play a crucial role in tumor-immune system interaction. The gene tr anscription of interleukin(IL)-2, IL-4, IL-7, IL-10 and interferon(IFN )-gamma of lymphocyte infiltrated, freshly excised tumor specimens fro m 10 renal cell carcinomas and 6 melanomas were investigated by revers e polymerase chain reaction (PCR) technique. Autologous, peripheral mo nonuclear cells (PBMC) and healthy tissue of the affected organs serve d as controls. In all samples the transcription of the beta-actin gene as a methodological control turned out to be positive. In contrast, n o cytokine gene transcription was detected in healthy tissue specimens and PBMC. IL-2 transcripts were detectable in no melanomas but in hal f of the renal tumor samples. IL-10 never transcribed in melanomas but was positive in 7 out of 10 renal cell carcinomas. In only 2 respecti vely 1 of the resected tissue probes was transcription of IL-4 and IFN -gamma detected. IL-7 was positive in 1 melanoma and in 6 urological n eoplasias. The most impressive fact is the frequent transcription of t he inhibiting factor IL-10 in renal cell carcinomas (7/10). This patte rn of cytokine gene transcription may explain functional deficits of T IL. At the time of surgery there exists only a partial and (for an ant igen driven stimulation) uncharacteristic activation of TIL, probably based on stimulating and inhibiting signals in the molecular tumor env ironment. For future immunotherapies this pattern of cytokine gene tra nscription offers novel approach routes.