Study of regulatory T-cells in patients with gastric malt lymphoma: influence on treatment response and outcome

Abstract

Purpose: FOXP3+ regulatory T cells (Treg) play an essential role in modulating host responses to tumors and infections. The role of these cells in the pathogenesis of MALT lymphomas remains unknown. The aims of the study were to quantify the number of infiltrating FOXP3+ and CD3+ cells in patients with gastric MALT lymphoma at diagnosis and to study kinetics of these cells and CD20+ tumor cells after treatment and during long-term follow-up.

Methods: FOXP3+, CD3+ and CD20+ cells were analyzed by immunohistochemistry and the number of cells was quantified using a micrometric ocular. Samples of 35 patients with gastric MALT lymphoma at diagnosis and after treatment were included. Diagnostic samples were compared to 19 cases of chronic gastritis and diffuse large B-cell lymphoma (DLBCL) of the stomach.

Results: The median number of FOXP3+ infiltrating cells was higher (27 cells/cm(2)) in gastric MALT patients than in DLBCL (10 cells; p = 0.162) but similar to chronic gastritis (20 cells; p = 0.605). No characteristic or specific distribution pattern of infiltrating FOXP3+ cells was found. Gastric MALT lymphoma patients responding to bacterial eradication therapy had higher number of FOXP3+ cells at study entry. Kinetics of both infiltrating FOXP3+ cells and tumor CD20+ cells were strongly dependent on the treatment administered.

Discussion: Gastric MALT lymphomas have a number of Treg cells more similar to chronic gastritis than to DLBCL. Patients with higher number of tumor infiltrating FOXP3+ cells at study entry seem to have better response to antibiotics. Kinetics of Treg and tumor cells are influenced by type of treatment.

Figure 1. Immunohistochemistry for CD20 and FOXP3 at study entry and at first response evaluation (1–2 months after finishing treatment).

Gastric biopsies samples from 4 gastric MALT lymphoma patients treated with different schedules. HP: erradication therapy alone; RQ: Rituximab+CHOP; RF: Rituximab+Fludarabine; RB: Rituximab+Bendamustine.

Figure 2. Kinetics of CD3+, FOXP3+, ratio FOXP3+/CD3+ and CD20+ cells by immunohistochemistry in responding patients.

Median CD20+ cells were significantly different between cases treated with antibioticis and those treated with fludarabine or bendamustine with or without Rituximab at first response evaluation (p = 0.001) but not later during follow-up.