T-cell levels are prognostic in mantle cell lymphoma

Clin Cancer Res. 2014 Dec 1;20(23):6096-104. doi: 10.1158/1078-0432.CCR-14-0889. Epub 2014 Oct 7.

Abstract

Purpose: The purpose of this study was to investigate the impact of T-cell subsets on pathologic and clinical features including disease outcome in mantle cell lymphoma (MCL).

Experimental design: Cell populations were investigated using flow cytometry in diagnostic MCL (n = 153) and reactive (n = 26) lymph node biopsies. Levels of tumor cells, T cells, T-cell subsets, and the CD4:CD8 ratio were assessed and related to pathologic and clinical parameters.

Results: MCL cases with diffuse and nodular histologic subtypes showed lower levels of T cells, especially CD4(+) T cells, than those with mantle zone growth pattern. Both CD3 and CD4 levels were lower in the nodular subtype than in mantle zone (P = 0.007; P = 0.003) and in the diffuse compared with the nodular subtype (P = 0.022; P = 0.015). The CD4:CD8 ratios were inversely correlated to tumor cell proliferation (P = 0.003). Higher levels of CD3(+) and CD4(+) T cells and higher CD4:CD8 ratios were associated with indolent disease (P = 0.043, 0.021, and 0.003 respectively). In univariate analysis, a high CD4:CD8 ratio, but not the histologic subtype, was correlated to longer overall survival (OS). In multivariate analysis, the CD4:CD8 ratio correlated with OS independently of Mantle Cell Lymphoma International Prognostic Index (MIPI) and high p53 expression (P = 0.023).

Conclusion: CD3(+), CD8(+), and particularly CD4(+) T-cell levels are higher in indolent MCL and decrease with more aggressive histology as reflected by a diffuse growth pattern. High CD4:CD8 ratio correlated independently of other high-risk prognostic factors with longer OS, suggesting a prognostic role for T cells in MCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-CD8 Ratio
  • Female
  • Humans
  • Immunophenotyping
  • Lymph Nodes / pathology
  • Lymphocyte Count
  • Lymphoma, Mantle-Cell / diagnosis
  • Lymphoma, Mantle-Cell / immunology*
  • Lymphoma, Mantle-Cell / mortality*
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Registries
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology