Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness.
Production of cytokines (CKs) in the tumor micro-environment may modulate tumor-host interactions. However, pre-clinical models often provide conflicting data and there is no established role for CKs as modulators of the natural or treatment-related behavior of tumors. Serial sampling by fine-needle aspirates (FNAs) of identical metastases from patients affected with metastatic melanoma and undergoing IL-2-based vaccination allowed prospective measurement of IL-10, TGF-beta1, TGF-beta2 and IFN-gamma transcriptional levels assessed by quantitative real-time PCR. Thus, it was possible to prospectively 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 treatment and 1 demonstrated >50% shrinkage. These regressions occurred after the follow-up FNA had been obtained. IL-10 transcript was differentially expressed in pre-treatment FNA of responding lesions (t-test p(2) = 0.002). During treatment, INF-gamma transcript levels significantly increased in regressing compared to non-regressing lesions (t-test p(2) = 0.03). These data suggest 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 characteristics of an effective immune response.
Mocellin
S
S
Department of Transfusion Medicine, Clinical Center, National Cancer Institute, National Institutes of Health, 10 Center Drive MSC 1502, Bethesda, MD 20892, USA.
Ohnmacht
G A
GA
Wang
E
E
Marincola
F M
FM
D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007109:Immunity; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D012330:RNA, Double-Stranded / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D016207:Cytokines; D012330:RNA, Double-Stranded