Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia

Acta Haematol. 2015;134(4):255-62. doi: 10.1159/000430980.

Abstract

Background: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment.

Methods: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL.

Results: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PDL1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide.

Conclusion: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis*
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Programmed Cell Death 1 Receptor / biosynthesis

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor