Outcome in Hodgkin's lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells

Clin Cancer Res. 2005 Feb 15;11(4):1467-73. doi: 10.1158/1078-0432.CCR-04-1869.

Abstract

Purpose: Recent studies of Hodgkin's lymphoma (HL) have suggested that the presence of regulatory T cells in the reactive background may explain the inhibition of the antitumoral host immune response observed in these patients. This study aimed to assess the relevance of regulatory T cells and CTLs present in the background of HL samples in the prognosis of a series of classic HL (cHL) patients.

Experimental design: Expression of granzyme B and TIA-1 (markers for CTL) and FOXP3 (a marker for regulatory T cells) were evaluated independently by immunohistochemistry in tissue microarrays of 257 cHL patients and correlated with patient outcome.

Results: The combined influence of the presence of FOXP3(+) and TIA-1(+) cells distinguished three risk groups of patients with 5-year overall survival of 100%, 88%, and 73%. The presence of a small number of FOXP3(+) cells and a high proportion of TIA-1(+) cells in the infiltrate represent an independent prognostic factor that negatively influenced event-free survival and disease-free survival in cHL. Compared with the features at diagnosis, relapsed samples tended to have more TIA-1(+) cells and a lower proportion of FOXP3(+) cells in the reactive background.

Conclusions: These data suggest that low infiltration of FOXP3(+) cells in conjunction with high infiltration of TIA-1(+) cells in cHL may represent biological markers predicting an unfavorable outcome. Moreover, the variation of these markers over the course of the disease implies a possible role for them in the progression of HL cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • DNA-Binding Proteins / analysis
  • Female
  • Forkhead Transcription Factors
  • Granzymes
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Poly(A)-Binding Proteins
  • Prognosis
  • Proteins / analysis
  • RNA-Binding Proteins
  • Serine Endopeptidases / analysis
  • Survival Analysis
  • T-Cell Intracellular Antigen-1
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / pathology*
  • T-Lymphocytes, Cytotoxic / chemistry
  • T-Lymphocytes, Cytotoxic / pathology*

Substances

  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Poly(A)-Binding Proteins
  • Proteins
  • RNA-Binding Proteins
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases