The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma

BACKGROUND: Multiple myeloma (MM) is an immunoproliferative disease characterised by the uncontrolled proliferation of plasma cells, which is accompanied by defects in the immune system. METHODS: This study aimed to characterise the frequency of T regulatory cells (Tregs), dendritic cells (DCs) as well as sub-populations of T cells bearing regulatory properties like CD4(+)GITR(+), CD4(+)CD62L(+), CD3(+)TCR gamma delta(+) along with the concentrations of IL-10, TGF beta, IL-6 in 66 patients with MM. Subsequently, the influence of therapy on those components of immune system was assessed. RESULTS: The percentage of both myeloid and plasmacytoid DC was lower in MM compared with control group while Treg (CD4(+)CD25(high)FOXP3(+)) frequencies were significantly higher in MM patients compared with healthy control (6.16% vs 0.05%, respectively). Also, the percentages of CD4(+)GITR(+), CD4(+)CD62L(+) were increased compared with healthy volunteers. We found that patients with higher percentages of Treg live shorter (median overall survival 21 months vs not-reached, P=0.013). CONCLUSION: This study identifies several abnormalities of immune system in MM, which only partly could be normalised after successful therapy. The dysfunction of immune system such as decreased antigen presentation along with increased frequencies of suppressive cells and cytokines might facilitate progression of the disease and infectious complications limiting survival of MM patients. British Journal of Cancer (2012) 106, 546-552. doi: 10.1038/bjc.2011.575 www.bjcancer.com Published online 5 January 2012 (C) 2012 Cancer Research UK