Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies

Table 1

Most relevant published studies investigating frequency, function, and prognostic significance of Tregs in CLL.

Reference	Patients/controls evaluated	Samples tested	Marker panel used in Treg evaluation by flow cytometry	Treg frequency	Functional studies	Impact on prognosis
Beyer et al. [34]	CLL/controls	PB	CD4/CD25	Increased	Reduced inhibitory function	Extended disease (Binet stage)
Giannopoulos et al. [73]	CLL/controls	PB	CD4/CD25/FoxP3	Increased	Not performed	Binet stage
Jak et al. [22]	CLL/controls	PB	CD4/CD25/CD127	Increased	More resistant to drug-inducedapoptosis than controls	Not evaluated
D’Arena et al. [23, 24]	CLL/controls	PB	CD4/CD25/CD127	Increased with a gradual variation from normal subjects to clinical MBL to CLL	Not performed	Rai stage, lymphocytosis, LDH, first time to treatment
Weiss et al. [25]	CLL/controls	PB	CD4/CD25/FoxP3	Increased	Not performed	Unmutated IgVH, CD38, chromosomal aberrations
Lad et al. [26]	CLL/controls	PB and FNA	CD4/CD25/CD127/IL-10	Reduced both Treg and IL-10 expressing Treg; higher absolute number	Not performed	Correlation with LDT (Tregs but not CD45RA^+ Tregs and CD8^+ Tregs were lower in CD38^+ZAP70^+ CLL group (with respect to CD38^−ZAP70^−)
Biancotto et al. [27]	CLL/controls	PB	CD4/CD25/FoxP3	Increased	Slightly reduced suppressive activity	Correlation with ZAP-70 and CD38 expression
Dasgupta et al. [28]	CLL/controls	PB	CD4/CD25/CD127/FoxP3	Increased	Not performed	Correlated with ZAP70 and CD38 expression
Mpakou et al. [29]	CLL/controls	PB	CD4/CD25/CD127	Increased	Suppression of T effector cells	Advanced stage
D’Arena et al. [30]	Clinical MBL/CLL/controls	PB	CD4/CD25/CD127	Reduced as % but increased as absolute number with a gradual variation from normal subjects to clinical MBL to CLL	Not performed
Rissiek et al. [31]	MBL/CLL/controls	PB	CD4/CD25/CD127/CD39	Expansion.; Highly suppressive CD39^+ Treg subset increased in all disease stages	Increasingly suppressive regulatory function initiating at MBL stage; effector function impairment after transition to CLL; partially recovered after chemo-immunotherapy	Shorter time to treatment

Increased at diagnosis; significantly reduced after fludarabine therapy. CLL: chronic lymphocytic leukemia; MBL: monoclonal B cell lymphocytosis; PB: peripheral blood; FNA: fine needle aspiration; LDT: lymphocyte doubling time.