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Soluble programmed cell death protein 1 (sPD-1) and the soluble programmed cell death ligands 1 and 2 (sPD-L1 and

Julie B Mortensen1, Ida Monrad1, Marie B Enemark1

  • 1Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.

European Journal of Haematology
|March 15, 2021
PubMed
Abstract

Insights

Soluble programmed cell death protein 1 (sPD-1) and soluble PD-L2 levels are elevated in lymphoma patients. Higher sPD-1 correlates with adverse prognostic factors, suggesting potential clinical utility in immunotherapy targeting the PD-1 pathway.

Area of Science:

  • Immunology
  • Oncology
  • Biochemistry

Background:

  • The programmed cell death protein 1 (PD-1) pathway is crucial for immune regulation and is often exploited by cancers to evade immune responses.
  • Soluble forms of PD-1 (sPD-1) and its ligands (sPD-L1/sPD-L2) are present in blood, but their clinical significance in lymphoma remains largely unknown.

Purpose of the Study:

  • To investigate the biological and clinical significance of soluble PD-1, PD-L1, and PD-L2 (sPD-1, sPD-L1, sPD-L2) in various lymphoma subtypes.
  • To explore the association of these soluble immune checkpoint molecules with prognostic factors and lymphoma characteristics.

Main Methods:

  • Serum samples from 131 lymphoma patients and 22 healthy individuals were analyzed.
  • Time-resolved immunofluorometric assay (TRIFMA) and enzyme-linked immunosorbent assay (ELISA) were employed to quantify sPD-1, sPD-L1, and sPD-L2 levels.

Main Results:

  • Lymphoma patients exhibited significantly higher serum levels of sPD-1 and sPD-L2 compared to healthy controls.
  • Elevated sPD-1 levels were associated with higher International Prognostic Index scores in diffuse large B-cell lymphoma.
  • Follicular lymphoma showed distinct patterns of higher sPD-1 and lower sPD-L1 levels, along with reduced ligand/receptor ratios, compared to other lymphoma types.

Conclusions:

  • This study provides the first comprehensive characterization of pretherapeutic sPD-1, sPD-L1, and sPD-L2 across diverse lymphoma subtypes.
  • The correlation of higher sPD-1 with adverse prognostic factors suggests a potential role in disease progression and clinical utility for immunotherapy.
  • Differential expression patterns, particularly in follicular lymphoma, may offer valuable biological insights for PD-1 pathway-targeted immunotherapies.
Keywords:
B7-H1 antigenHodgkin diseaseNon-Hodgkinlymphomaprogrammed cell death 1 receptorprogrammed cell death ligand 2 proteinserum

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