Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia

Leuk Res. 2018 Sep;72:113-119. doi: 10.1016/j.leukres.2018.08.006. Epub 2018 Aug 10.

Abstract

There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib. We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL cells, T cells and monocytes. The immunophenotyping of CLL and immune cells in peripheral blood was performed on 16 high-risk CLL patients treated with ibrutinib. After early ibrutinib administration, the HLA-DR expression on CLL cells reduced (P = 0.032), accompanied by an increase in CLL cell counts in peripheral blood (P = 0.001). In vitro culturing of CLL cells with ibrutinib also revealed the reduction in the HLA-DR expression at protein and mRNA levels (P < 0.01). The decrease in HLA-DR on CLL cells after the first month was followed by the gradual increase of its expression by the 12th month (P = 0.001). A one-month follow-up resulted in elevated absolute counts of CD4+ (P = 0.002) and CD8+ (P < 0.001) T cells as well as CD4+ and CD8+ cells bearing HLA-DR (P < 0.01). The long-term administration of ibrutinib was associated with the increased numbers of CD4+ bearing HLA-DR (P = 0.006) and elevation of HLA-DR expression on all monocyte subsets (P ≤ 0.004). Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells and monocytes. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.

Keywords: CLL cells; Chronic lymphocytic leukemia; HLA-DR; Ibrutinib; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Aged
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Gene Expression Regulation, Leukemic / drug effects*
  • HLA-DR Antigens / biosynthesis*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell* / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Piperidines
  • Pyrazoles / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Time Factors

Substances

  • HLA-DR Antigens
  • Neoplasm Proteins
  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine