Research Article

Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain Significance and Multiple Myeloma: In Search of a Role

Table 2

Most relevant published studies investigating the frequency and prognostic significance of Tregs in MM compared with the present study.

ReferencePatients/controls evaluatedSamples testedMethod used in Treg evaluationTregs frequencyFunctional studiesImpact on prognosis

Prabhala et al. [5]MGUS
MM
Controls
Isolated PBMCCD4+FoxP3+DecreasedUnable to suppress anti-CD3-mediated T-cell proliferationNot evaluated

Beyer et al. [6]MGUS
MM
Controls
Isolated PBMCCD4+CD25FoxP3+
(% of CD4+ cells)
Increased in MM versus MGUS (trend without statistical significance)Strong inhibitory functionNot evaluated

Feyler et al. [7]MGUS
MM
Controls
Isolated PBMC and BMCD4+CD25+FoxP3+Increased in PBMC but not in BMNot evaluatedCorrelation with disease burden (paraprotein)

Gupta et al. [8]MMIsolated PBMCCD4+CD25+CD127FoxP3+
(% of CD4+ cells)
Reduced in untreated which increased after treatment with lenalidomideAble to inhibit proliferation of CD4+CD25-T-cellsIncrease of Tregs in responding patients to therapy; decrease correlates with ISS I + II

Muthu Raja et al. [9]MGUS
SMM
MM
PB/BM wholeCD4+CD25+CD127-CD45RA+/−
(% of CD4 cells)
Increased in MM but not in SMM and MGUSAble to inhibit the proliferation of CD4+ T-cells and the secretion of IFN-Correlation with adverse clinical features (hypercalcemia, lower normal PC, and IgA subtype); no correlation with ISS; predict time to progression; MM patients with ≥5% of Tregs had inferior time to progression

Giannopoulos et al. [10]MM
Controls
Isolated PBMCCD4+CD25FoxP3+IncreasedNot evaluatedCorrelation with shorter overall survival

Foglietta et al. [11]MM
MGUS
Controls
Isolated freshly PB and frozen BMCD4+CD25FoxP3+SimilarEffective suppressor functionNo correlation with the pattern of BM infiltration

Present studyMM
MGUS
Controls
PB
whole
CD4+CD25CD127
(% and absolute number)
SimilarEffective suppressor functionNo correlation with laboratory and clinical variables; no correlation with outcome

BM: bone marrow; PB: peripheral blood; PBMC: peripheral blood mononuclear cells; MM: multiple myeloma; SMM: smoldering multiple myeloma; MGUS: monoclonal gammopathies of uncertain significance.