Review Article

Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies

Table 3

Most relevant published studies investigating the frequency and the prognostic significance of Tregs in monoclonal gammopathies.

ReferencePatients/controls evaluatedSamples testedMarker panel used in Treg evaluation by flow cytometryTreg frequencyFunctional studiesImpact on prognosis

Prabhala et al. [50]MGUS/MM/controlsPBMCCD4/FoxP3DecreasedUnable to suppress anti-CD3-mediated T cell proliferationNot evaluated
Beyer et al. [52]MGUS/MM/controlsPBMCCD4/CD25/FoxP3 (% of CD4+ cells)Increased in MM versus MGUS (trend without statistical significance)Strong inhibitory functionNot evaluated
Feyler et al. [53]MGUS/MM/controlsPBMC and BMCD4/CD25/FoxP3Increased in PBMC but not in BMNot evaluatedCorrelation with disease burden (paraprotein)
Gupta et al. [54]MMPBMCCD4/CD25/CD127/FoxP3 (% 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 correlation with ISS I + II
Muthu Raja et al. [55]MGUS/SMM/MMPB/BM wholeCD4/CD25/CD127/CD45RA (% of CD4+ cells)Increased in MM but not in SMM and MGUSAble to inhibit proliferation of CD4+ T cells and the secretion of IFN-γCorrelation 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
Giannopulos et al. [56]MM/controlsPBMCCD4/CD25/FoxP3IncreasedNot evaluatedCorrelation with shorter overall survival
Foglietta et al. [57]MM/MGUS/controlsFresh PB and frozen BMCD4/CD25/FoxP3SimilarEffective suppressor functionNo correlation with the pattern of BM infiltration
D’Arena et al. [51]MM/MGUS/controlsPB wholeCD4/CD25/CD127 (% and absolute number)SimilarEffective suppressor functionNo correlation with laboratory and clinical variables; no correlation with outcome

MM: multiple myeloma; MGUS: monoclonal gammopathy of uncertain significance; SMM: smoldering multiple myeloma; ISS: international staging system; PB: peripheral blood; PBMC; peripheral blood mononuclear cells; BM: bone marrow.