Low number of intrafollicular T cells may predict favourable response to rituximab-based immuno-chemotherapy in advanced follicular lymphoma: a secondary analysis of a randomized clinical trial

J Cancer Res Clin Oncol. 2019 Aug;145(8):2149-2156. doi: 10.1007/s00432-019-02961-9. Epub 2019 Jul 4.

Abstract

Background: First-line rituximab therapy together with chemotherapy is the standard care for patients with advanced follicular B-cell lymphoma, as rituximab together with chemotherapy prolongs progression-free and overall survival (Herold et al. 2007; Marcus et al. 2005). However, as not all patient subgroups benefit from combined immuno-chemotherapy, we asked whether the microenvironment may predict benefit from rituximab-based therapy.

Design: To address this question, we performed a retrospective immunohistochemical analysis on pathological specimens of 18 patients recruited into a randomized clinical trial, where patients with advanced follicular lymphoma were randomized into either chemotherapy or immuno-chemotherapy with rituximab (Herold et al. 2007).

Results: We show here that rituximab exerts beneficial effects, especially in the subgroup of follicular lymphoma patients with low intrafollicular CD3, CD5, CD8, and ZAP70 and high CD56 and CD68 expression.

Conclusion: Rituximab may overcome immune-dormancy in follicular lymphoma in cases with lower intrafollicular T-cell numbers and higher CD56 and CD68 cell counts. As this was a retrospective analysis on a small subgroup of patients, these data need to be corroborated in larger clinical trials.

Keywords: Follicular lymphoma; Macrophages; Microenvironment; NK cells; Rituximab; T cells.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chlorambucil / administration & dosage
  • Female
  • Humans
  • Immunotherapy
  • Killer Cells, Natural / pathology
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Lymphoma, Follicular / diagnosis*
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / immunology*
  • Lymphoma, Follicular / pathology
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Prednisone / administration & dosage
  • Prognosis
  • Retrospective Studies
  • Rituximab / administration & dosage*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology*
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Chlorambucil
  • Rituximab
  • Mitoxantrone
  • Prednisone