Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness

Production of cytokines (CKs) in the tumor micro-environment may modulate t umor-host interactions. However, preclinical models often provide conflicti ng data and there is no established role for CKs as modulators of the natur al or treatment-related behavior of tumors. Serial sampling by fine-needle aspirates (FNAs) of identical metastases from patients affected with metast atic melanoma and undergoing IL-2-based vaccination allowed prospective mea surement of IL-10, TGF-beta1, TGF-beta2 and IFN-gamma transcriptional level s assessed by quantitative real-time PCR, Thus, it was possible to prospect ively document the expression of markers relevant to a given treatment and follow at the same time the clinical outcome of the lesions left in place. Eight of 27 metastatic lesions completely regressed in response to the trea tment and I demonstrated >50% shrinkage, These regressions occurred after t he follow-up FNA had been obtained. IL-10 transcript was differentially exp ressed in pre-treatment FNA of responding lesions (t-test p(2) = 0.002). Du ring treatment, INF-gamma transcript levels significantly increased in regr essing compared to non-regressing lesions (t-test P-2 = 0.03), These data s uggest that the pre-treatment CK profile of the tumor micro-environment may determine clinical responsiveness to immune therapy. Furthermore, temporal changes in CK expression during treatment might describe the biological ch aracteristics of an effective immune response. Published 2001 Wiley-Liss, I nc.