HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma

Arch Immunol Ther Exp (Warsz). 2016 Jun;64(3):225-40. doi: 10.1007/s00005-015-0372-8. Epub 2015 Dec 14.

Abstract

The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.

Keywords: Diffuse large B-cell lymphoma; Human leukocyte antigen-G; Immunohistochemistry; Major histocompatibility class II; Outcome.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • HLA-G Antigens / immunology*
  • HLA-G Antigens / metabolism
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunohistochemistry
  • Immunotherapy / methods
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Probability
  • Prognosis
  • Regression Analysis
  • Remission Induction
  • Rituximab
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • HLA-G Antigens
  • Histocompatibility Antigens Class II
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • COP protocol 2