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Blood, 1 January 2006, Vol. 107, No. 1, pp. 301-304.
Prepublished online as a Blood First Edition Paper on September 8, 2005; DOI 10.1182/blood-2005-08-3101.
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Submitted August 2, 2005
Accepted August 23, 2005
Dysfunctional T regulatory cells in multiple myeloma
Rao H Prabhala, Paola Neri, Jooeun E Bae, Pierfrancesco Tassone, Masood A Shammas, Charles K Allam, John F Daley, Dharminder Chauhan, Elizabeth Blanchard, Hemant S Thatte, Kenneth Anderson, and Nikhil C Munshi*
VA Boston Healthcare System, Boston, MA, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
VA Boston Healthcare System, Boston, MA, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; University of "Magna Graecia" and Cancer Center, Catanzaro, Italy
VA Boston Healthcare System, Boston, MA, USA
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
* Corresponding author; email: nikhil_munshi{at}dfci.harvard.edu.
Multiple myeloma (MM) is characterized by production of monoclonal immunoglobulin with associated suppressed uninvolved immunoglobulins and dysfunctional T cell responses. The biological basis of this dysfunction remains ill defined. Since T regulatory (Treg) cells play an important role in suppressing normal immune responses, we have here evaluated the potential role of Treg cells in immune dysfunction in MM. We have observed a significant increase in CD4+CD25+ T cells in monoclonal gammopathy of undetermined significance (MGUS) and MM compared to normal donors (25% and 26% versus 14% respectively); however, the Treg cells as measured by Foxp3 expression are significantly decreased in both MGUS and MM compared to normal donors. Moreover, Treg cells in MM and MGUS are unable to suppress anti-CD3-mediated T cell proliferation even when added in higher proportion. This decreased number and function of Treg cells in MGUS and in MM, at least in part may be responsible for non-specific increase in CD4+CD25+ T cells leading to dysfunctional T cell responses.
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