Frequency of circulating tregs with demethylated FOXP3 intron 1 in melanoma patients receiving tumor vaccines and potentially treg-depleting agents

I. Jolanda M De Vries, Chiara Castelli, Caroline Huygens, Joannes F M Jacobs, Julie Stockis, Beatrice Schuler-Thurner, Gosse J. Adema, Cornelis J A Punt, Licia Rivoltini, Gerold Schuler, Pierre G. Coulie, Sophie Lucas

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Regulatory T cells (Tregs) are thought to inhibit antitumor immune responses, and their depletion could therefore have a synergistic effect with therapeutic cancer vaccines. We investigated the impact of three medications on blood Treg frequency in vaccinated cancer patients. Experimental Design: To date, the most specific marker for human Tregs is demethylation in the DNA that encodes the transcription factor FOXP3. Thus, we used a FOXP3 methylation-specific quantitative PCR assay (MS-qPCR) to measure Treg frequencies in the peripheral blood mononuclear cells (PBMCs) of melanoma patients. The patients participated in three clinical trials that combined tumor vaccines with potential Treg-depleting agents: low-dose cyclophosphamide, anti-CD25 monoclonal antibody daclizumab, and the IL-2/diphtheria toxin fusion protein denileukin diftitox. Results: In the nine control patients, blood Treg frequencies varied over time; there was a 46% reduction in one patient. In treated patients, a more than 2-fold decrease in Tregs was observed in one out of 11 patients receiving cyclophosphamide and in four out of 13 receiving daclizumab, but there was no such Treg decrease in any of the six patients who received denileukin diftitox. As a positive control, a more than 2-fold increase in blood Tregs was detected in four out of nine patients who were treated with interleukin-2. Conclusions: We used a MS-qPCR method that detects Tregs but not other activated T lymphocytes; however, none of the Treg-depleting strategies that we tested led, in the majority of patients, to a conservative 50% reduction in blood Tregs.

Original languageEnglish
Pages (from-to)841-848
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number4
DOIs
Publication statusPublished - Feb 15 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Frequency of circulating tregs with demethylated FOXP3 intron 1 in melanoma patients receiving tumor vaccines and potentially treg-depleting agents'. Together they form a unique fingerprint.

Cite this