Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness

Simone Mocellin, Galen A. Ohnmacht, Ena Wang, Francesco M. Marincola

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56 Citations (Scopus)

Abstract

Production of cytokines (CKs) in the tumor micro-environment may modulate tumor-host interactions. However, preclinical 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-β1, TGF-β2 and IFN-γ 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 I 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 p2 = 0.002). During treatment, INF-γ transcript levels significantly increased in regressing compared to non-regressing lesions (t-test p2 = 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.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalInternational Journal of Cancer
Volume93
Issue number2
DOIs
Publication statusPublished - 15 Jul 2001

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Keywords

  • Cytokine
  • Fine-needle aspiration
  • Immune response
  • Melanoma
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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