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

PLoS One. 2012;7(12):e51681. doi: 10.1371/journal.pone.0051681. Epub 2012 Dec 19.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism
  • Gastritis / drug therapy
  • Gastritis / immunology*
  • Gastritis / pathology
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter pylori
  • Humans
  • Immunoenzyme Techniques
  • Lymphoma, B-Cell, Marginal Zone / drug therapy
  • Lymphoma, B-Cell, Marginal Zone / immunology*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / immunology*
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Familial primary gastric lymphoma

Grants and funding

This work received grant support from Instituto de Salud Carlos III, Spanish Ministry of Science and Technology grant (FIS-FEDER 07/0586). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.