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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
Author(s) -
Bjoern J.,
Brimnes M. K.,
Andersen M. H.,
thor Straten P.,
Svane I. M.
Publication year - 2011
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2010.02494.x
Subject(s) - foxp3 , peripheral blood mononuclear cell , il 2 receptor , medicine , regulatory t cell , interleukin 7 receptor , immunology , immunotherapy , melanoma , dendritic cell , t cell , immune system , cancer research , biology , in vitro , biochemistry
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 high , 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 CD4 + CD25 high 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 CD4 + CD25 high 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 CD4 + CD25 high CD127 − 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.