Myeloma skews regulatory T and pro-inflammatory T helper 17 cell balance in favor of a suppressive state

Abstract

Discrepancies in the literature between regulatory T cell (T_reg) and pro-inflammatory T helper 17 (T_h17) numbers in multiple myeloma (MM) can be largely explained by technical differences in methodology and patient selection. In this study, T_reg cells were defined as CD3⁺CD4⁺CD25⁺⁺CD127^lo cells. Patients with MM (n = 20) had a significant imbalance in T_reg/T_h17 ratio when compared with either aged-matched controls (n = 28) or other monoclonal gammopathies, and this was associated with a significantly worse survival. The percent T_reg in bone marrow of patients with MM was higher than that in matched peripheral blood samples (p = 0.02), although FOXP3 expression within bone marrow T cells was lower (p = 0.02). We observed increased T_reg function, both in vivo and in vitro, due at least partially to an increase in CTLA-4 expression by concurrent treatment with dexamethasone and immune modulatory compounds (iMiDs). We suggest that immunoregulatory balance is important during active chemotherapy and that conclusions related to the immunostimulatory effect of iMiDs based on in vitro testing must be considered with caution.

Keywords::

• Multiple myeloma
• T_reg cells
• immunoregulation
• IMiDs
• dexamethasone

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

We acknowledge financial support from the Sydney Foundation for Medical Research and the Cancer Institute of New South Wales.