Comparative methodologies of regulatory T cell depletion in a murine melanoma model

Matsushita, Norimasa, Pilon-Thomas, Shari A., Martin, Lisa M. and Riker, Adam I. (2008) Comparative methodologies of regulatory T cell depletion in a murine melanoma model. Journal of Immunological Methods, 333 1-2: 167-179. doi:10.1016/j.jim.2008.01.012

Author Matsushita, Norimasa
Pilon-Thomas, Shari A.
Martin, Lisa M.
Riker, Adam I.
Title Comparative methodologies of regulatory T cell depletion in a murine melanoma model
Journal name Journal of Immunological Methods   Check publisher's open access policy
ISSN 0022-1759
Publication date 2008-04
Sub-type Article (original research)
DOI 10.1016/j.jim.2008.01.012
Volume 333
Issue 1-2
Start page 167
End page 179
Total pages 13
Place of publication Netherlands
Publisher Elsevier BV
Language eng
Abstract There has been recent interest in the depletion of regulatory T cells (Tregs) as part of a multi-facete approach to the immunotherapy of melanoma patients. This is in part due recent findings that convincingly show that Tregs are an integral part of regulating and even suppressing an immune response to growing tumor cells. We therefore compared three methods of Treg depletion and/or elimination, utilizing low dose cyclophosphamide (CY), a specific antibody directed against the IL-2 receptor found on Tregs (PC61) and the use of denileukin diftitox (DD), which is a fusion protein designed to have a direct cytocidal action on cells which express the IL-2 receptor. We show that CY administration resulted in the highest reduction in Tregs among the three reagents. However, the reduction in Tregs with CY was also associated with the concomitant reduction of CD8(+) T cells and a lack of tumor antigen priming. Utilization of DD resulted in a > 50% Treg cell reduction without parallel cytocidal effects upon other T cell subsets but did not enhance anti-tumor immunity against B16 melanoma. Lastly, the PC61 showed a moderate reduction of Tregs that lasted longer than the other reagents, without a reduction in the total number of CD8(+) T cells. Furthermore, PC61 treatment did not abrogate tumor antigen-specific immunity elicited by dendritic cells (DC). We therefore conclude that PC61 administration was the most effective method of reducing Tregs in a murine melanoma model in addition to providing evidence of a synergistic effect when combined with DC-based immunotherapy.
Keyword Anti-CD25 antibody
Dendritic cell
Denileukin diftitox
Regulatory T cell
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 64 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 75 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 11 Sep 2011, 12:44:34 EST by System User on behalf of School of Medicine