Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial

Haematologica. 2015 Feb;100(2):238-45. doi: 10.3324/haematol.2014.113472. Epub 2014 Nov 7.

Abstract

The prognostic impact of the tumor microenvironment in diffuse large B-cell lymphoma has not been systematically assessed. We analyzed mRNA and antigen expression of monocytes, macrophages, lymphocytes, dendritic and natural killer cells in pretreatment tumor samples of patients with high-risk diffuse large B-cell lymphoma using gene expression microarray and immunohistochemistry. The patients were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. Of the studied markers for non-malignant inflammatory cells, CD68 expression and CD68(+) macrophage counts correlated with favorable outcome. Five-year progression-free survival rates were 83% and 43% for the patients with high and low CD68 mRNA levels, respectively (P=0.007), while overall survival rates were 83% and 64%, respectively (P=ns). The patients with high CD68(+) macrophage counts had better 5-year progression-free survival (74% versus 40%; P=0.003) and overall survival (90% versus 60%; P=0.009) than the patients with low macrophage counts. Low CD68(+) macrophage count retained its prognostic impact on overall survival with age-adjusted International Prognostic Index [RR=5.0 (95% CI 1.024-19.088); P=0.017]. The findings were validated in three independent cohorts of patients treated with chemoimmunotherapy. In contrast, in patients treated with chemotherapy, high CD68(+) macrophage count was associated with poor progression-free survival (40% versus 72%; P=0.021) and overall survival (39% versus 72%; P=0.015). Together, the data suggest that macrophages exhibit a dual, treatment-specific role in diffuse large B-cell lymphoma. For the patients treated with chemoimmunotherapy, high pretreatment CD68 mRNA levels and CD68(+) macrophage numbers predict a favorable outcome.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Immunotherapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / therapy*
  • Macrophages / immunology*
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal