T-Cell Levels Are Prognostic in Mantle Cell Lymphoma

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. Clin Cancer Res; 20(23); 6096–104. ©2014 AACR .