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Soluble PD-1 ligands regulate T-cell function in Waldenstrom macroglobulinemia.

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Cytokines like IL-21 and IL-6 increase soluble programmed death-1 (PD-1) ligands in Waldenstrom macroglobulinemia (WM). These soluble ligands impair T-cell function, potentially driving WM progression.

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Area of Science:

  • Immunology
  • Oncology
  • Hematology

Background:

  • Immune checkpoint molecules' role in Waldenstrom macroglobulinemia (WM) is unknown.
  • Bone marrow microenvironment cytokines contribute to WM pathobiology.

Purpose of the Study:

  • Investigate cytokine impact on immune regulation in WM.
  • Specifically examine interleukin-6 (IL-6) and interleukin-21 (IL-21) effects on programmed death-1 (PD-1) and its ligands (PD-L1, PD-L2).

Main Methods:

  • Assessed PD-L1 and PD-L2 gene and protein expression in WM cell lines and patient cells.
  • Measured soluble PD-1 ligand levels in patient plasma and serum.
  • Evaluated the functional impact of soluble PD-1 ligands on T-cells.

Main Results:

  • IL-21, interferon γ, and IL-6 induced PD-L1/PD-L2 gene expression in WM cells.
  • Elevated soluble PD-L1 and PD-L2 were found in WM patients.
  • Soluble PD-1 ligands inhibited T-cell proliferation and function.

Conclusions:

  • Soluble PD-1 ligands are elevated in WM and mediated by cytokines.
  • These ligands can impair T-cell function, suggesting a role in WM progression.