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European journal of haematology
Jul, 2021;107 (1): 81-91.

Soluble programmed cell death protein 1 (sPD-1) and the soluble programmed cell death ligands 1 and 2 (sPD-L1 and sPD-L2) in lymphoid malignancies.

Julie B Mortensen, Ida Monrad, Marie B Enemark, Maja Ludvigsen, Peter Kamper, Mette Bjerre, Francesco d'Amore
Author Information
  1. Julie B Mortensen: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark. ORCID
  2. Ida Monrad: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  3. Marie B Enemark: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  4. Maja Ludvigsen: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  5. Peter Kamper: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
  6. Mette Bjerre: Medical/SDCA Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  7. Francesco d'Amore: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
PMID: 33721375 DOI: 10.1111/ejh.13621

Abstract

BACKGROUND: The programmed cell death protein 1 (PD-1) and its ligand 1 and 2 (PD-L1/PD-L2) regulate the immune system, and the checkpoint pathway can be exploited by malignant cells to evade anti-tumor immune response. Soluble forms (sPD-1/sPD-L1/sPD-L2) exist in the peripheral blood, but their biological and clinical significance is unclear.
METHOD: Time-resolved immunofluorometric assay (TRIFMA) and enzyme-linked immunosorbent assay (ELISA) were used to measure sPD-1, sPD-L1, and sPD-L2 levels in serum from 131 lymphoma patients and 22 healthy individuals.
RESULTS: Patients had higher sPD-1 and sPD-L2 levels than healthy individuals. In diffuse large B-cell lymphoma, patients with high International Prognostic Index score had higher sPD-1 levels and sPD-L2 levels correlated with subtype according to cell of origin. Compared to other lymphoma types, follicular lymphoma displayed higher sPD-1 and lower sPD-L1 levels along with lower ligand/receptor ratios.
CONCLUSION: This is the first study to simultaneously characterize pretherapeutic sPD-1, sPD-L1, and sPD-L2 in a variety of lymphoma subtypes. The relation between higher sPD-1 levels and adverse prognostic factors suggests a possible biological role and potential clinical usefulness of sPD-1. Moreover, the reverse expression pattern in follicular lymphoma and T-cell lymphoma/leukemia may reflect biological information relevant for immunotherapy targeting the PD-1 pathway.

Keywords

B7-H1 antigen Hodgkin disease Non-Hodgkin lymphoma programmed cell death 1 receptor programmed cell death ligand 2 protein serum

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Grants

  1. /Fonden til Laegevidenskabens Fremme
  2. /Det Frie Forskningsråd
  3. /the Oticon Foundation
  4. /the Danish Lymphoma Group
  5. /Karen Elise Jensens Fond
  6. /The Maersk Foundation

MeSH Term

Adult
Apoptosis
B7-H1 Antigen
Biomarkers, Tumor
Blood Donors
Case-Control Studies
Cell Count
Diagnostic Tests, Routine
Enzyme-Linked Immunosorbent Assay
Female
Gene Expression Regulation, Leukemic
Humans
Immunotherapy
Leukemia
Ligands
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Male
Middle Aged
Prognosis
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor

Chemicals

B7-H1 Antigen
Biomarkers, Tumor
CD274 protein, human
Ligands
PDCD1 protein, human
PDCD1LG2 protein, human
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor
Journal Article

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