학술논문

Changes in Peripheral Blood Level of Regulatory T cells in Patients with Malignant Melanoma During Treatment with Dendritic Cell Vaccination and Low-dose IL-2.
Document Type
Article
Source
Scandinavian Journal of Immunology. Mar2011, Vol. 73 Issue 3, p222-233. 12p.
Subject
*MELANOMA
*T cell differentiation
*DENDRITIC cells
*CANCER immunotherapy
*VACCINATION
*INTERLEUKIN-2
*REDUCTION of drug dosage
*FORKHEAD transcription factors
*PATIENTS
Language
ISSN
0300-9475
Abstract
In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25, was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4CD25 T cell subset from 6% to 22% ( P < 0.001). At the 6th vaccine, a general decline was observed and a significantly ( P = 0.01) lower level of CD4CD25 Treg cells was reached in the group of patients who attained disease stabilization (9.5%) compared to patients with continued progressive disease (14.5%). However, when FoxP3 was employed for retrospective analysis of Tregs on frozen blood, this difference did not reach significance ( P = 0.09). The vast majority of the Treg produced IL-10 and, to a varying extent, TGF-β. In addition, sorted CD4CD25CD127 Tregs were able to suppress proliferation of peripheral blood mononuclear cells in a dose-dependent manner, thus suggesting a regulatory functionality. These findings emphasize the need for strategies to effectively eliminate Treg cells to optimize the clinical effectiveness of cancer immunotherapy. [ABSTRACT FROM AUTHOR]