T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab

Clin Cancer Res. 2011 Jun 15;17(12):4136-44. doi: 10.1158/1078-0432.CCR-11-0264. Epub 2011 Apr 25.

Abstract

Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.

Experimental design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a-rituximab combinations.

Results: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046).

Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8(+) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Interferon-alpha / therapeutic use
  • Lymphocyte Subsets / metabolism
  • Lymphoma, Follicular / diagnosis*
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Rituximab
  • Survival Analysis
  • T-Lymphocytes / metabolism*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Interferon-alpha
  • Rituximab