Loss of HLA-DR expression is related to tumor microenvironment and predicts adverse outcome in diffuse large B-cell lymphoma

Leuk Lymphoma. 2016;57(1):161-6. doi: 10.3109/10428194.2015.1038708. Epub 2015 May 18.

Abstract

The interaction between tumor cells and the tumor microenvironment is essential in the development and progression of diffuse large B-cell lymphoma (DLBCL). Loss of human leukocyte antigen DR (HLA-DR) in DLBCL is a robust adverse prognostic marker. We evaluated the immunohitochemical expression of HLA-DR in lymphoma and the biologic implications of the loss of HLA-DR. The loss of HLA-DR correlated with clinical stage (p < 0.05), International Prognosis Index (p < 0.05), soluble interleukin-2 receptor (p < 0.05) and poor outcome in patients with DLBCL, especially among elderly patients. Flow cytometry analysis of the infiltrating T-cells showed that the mean CD4 + CD25 +/CD8 ratio of the infiltrating T-cells was higher in the HLA-DR positive group than in the HLA-DR negative group (p < 0.05). These data suggest that loss of HLA-DR expression in DLBCL decreases the ratio of helper T-cell within the T-cell population in the tumor microenvironment and might contribute to escape from immunosurveillance.

Keywords: Diffuse large B-cell lymphoma; HLA-DR; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers
  • Female
  • Gene Expression
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / metabolism*
  • Humans
  • Immunophenotyping
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Phenotype
  • Prognosis
  • Survival Analysis
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology
  • Young Adult

Substances

  • Biomarkers
  • HLA-DR Antigens