Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies

Table 2

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

Reference	Patients/controls evaluated	Samples tested	Marker panel used in Treg evaluation by flow cytometry	Treg frequency	Functional studies	Impact on prognosis
Tzankov et al. [43]	Lymphomas	Node biopsy	FoxP3 (IHC)	Increased	Not performed	Correlation with disease-specific and failure-free survival in FL and disease-specific survival in germinal center-like DLBCL and OS and failure-free survival in classical HD, but negative prognostic effect in nongerminal center DLBCL. Independent prognostic significance for failure-free survival in classical HD and of borderline significance for OS in classical HD and disease-specific survival in germinal center-like and nongerminal center DLBCL
Alvaro et al. [44]	Classical HL	Node biopsy	FoxP3 (IHC)	Not reported	Not performed	Small number influenced negatively EFS and DFS
Schreck et al. [42]	Classical HL/hyperplastic tonsils	Node biopsy	FoxP3 (IHC)	Increased	Not performed	Increased DFS and EFS; high Tregs/Th2 ratio correlated with shortened DFS
Garcia et al. [45]	Gastric MALT lymphoma	Gastric biopsy	FoxP3 (IHC)	Increased with respect to DLBCL but similar to chronic gastritis	Not performed	Higher number correlated with response to antibacterial eradication therapy
Koreishi et al. [47]	Relapsed/refractory HL	Node biopsy	FoxP3 (tissue microarray)	Not reported	Not performed	Lower Tregs correlated with poor OS
Chang et al. [46]	DLBCL/normal	Node biopsy	CD4^+ CD25^+	Increased	Not performed	Higher with poor survival and IPI
Kim et al. [48]	Extranodal natural killer/T cell lymphoma	Node biopsy	FoxP3 (IHC)	Heterogenous expression	Not performed	The decreased number of Tregs was more common in patients with poor performance status or in those presented in nonupper aerodigestive tract. Patients with increased numbers of Tregs showed prolonged OS and PFS.
Carreras et al. [49]	FL at diagnosis and relapse	Node biopsy	FoxP3 (IHC)	Not reported	Not performed	Inversely correlated with OS. Patients with very low numbers of Tregs (<5%) presented more frequently with refractory disease. No correlation with FLIPI. Patients with transformed DLBCL had lower Treg percentages than FL grades 1, 2, or 3

HL: Hodgkin’s lymphoma; FL: follicular lymphoma; DLBCL: diffuse large B cell lymphoma; MALT: mucosa-associated lymphoid tissue; IHC: immunohistochemistry; OS: overall survival; DFS: disease-free survival, EFS: event-free survival.