Biology of Human Tumors T-Cell Levels Are Prognostic in Mantle Cell Lymphoma

نویسندگان

  • Lina Nygren
  • Agata M. Wasik
  • Stefanie Baumgartner-Wennerholm
  • Åsa Jeppsson-Ahlberg
  • Monika Klimkowska
  • Patrik Andersson
  • Daren Buhrkuhl
  • Birger Christensson
  • Eva Kimby
  • Birgitta Sander
چکیده

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 1⁄4 153) and reactive (n 1⁄4 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 CD4þ T cells, than those with mantle zone growth pattern. Both CD3 and CD4 levels were lower in the nodular subtype than in mantle zone (P1⁄4 0.007; P1⁄4 0.003) and in the diffuse compared with the nodular subtype (P 1⁄4 0.022; P 1⁄4 0.015). The CD4:CD8 ratios were inversely correlated to tumor cell proliferation (P 1⁄4 0.003). Higher levels of CD3þ and CD4þ T cells and higher CD4:CD8 ratios were associated with indolent disease (P 1⁄4 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 correlatedwithOS independently ofMantleCell Lymphoma International Prognostic Index (MIPI) and high p53 expression (P 1⁄4 0.023). Conclusion: CD3þ, CD8þ, and particularly CD4þ 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 factorswith longerOS, suggesting a prognostic role for T cells in MCL. Clin Cancer Res; 20(23); 6096–104. 2014 AACR.

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تاریخ انتشار 2014