Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mocellin, S; Ohnmacht, GA; Wang, E; Marincola, FM

Published Date

  • July 15, 2001

Published In

Volume / Issue

  • 93 / 2

Start / End Page

  • 236 - 242

PubMed ID

  • 11410872

Pubmed Central ID

  • 11410872

International Standard Serial Number (ISSN)

  • 0020-7136

Digital Object Identifier (DOI)

  • 10.1002/ijc.1328

Language

  • eng

Conference Location

  • United States