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Coinhibitory Molecule PD-1 as a Therapeutic Target in the Microenvironment of Multiple Myeloma

[ Vol. 17 , Issue. 9 ]

Author(s):

Djordje Atanackovic, Tim Luetkens, Sabari Radhakrishnan and Nicolaus KrogerPages 839-845 (7)

Abstract:


Background: Patients with Multiple Myeloma suffer from dysregulation of the immune system and new therapeutic options targeting the immune systems such as monoclonal antibodies or specific Cell therapy such as CAR-T cells have entered clinical practice, but the exhausted immune system hampered a more effective immunotherapy. Targeting the immunological dysfunction in the microenviroment might be a potential target for immune-mediated therapies.

Method: Here we review the current literature and knowledge about the programmed death 1 (PD-1) receptor which is expressed on the surface of exhausted T and B cells and its ligand PD-L1 is expressed on myeloma cells and inhibits T cell-mediated apoptosis.

Results: The programmed death 1 (PD-1) receptor is expressed on the surface of exhausted T and B cells and its ligand PD-L1 is expressed on myeloma cells and inhibits Tcell-mediated apoptosis. Inhibiting such “checkpoint” by monoclonal antibodies recently has been shown high activity in solid tumors and malignant lymphomas. In patients with multiple myelomaPD-L1 is overexpressed on myeloma cells and PD1 on T-cells suggesting an active role of PD-1/PD-L1 in the immunosuppressive microenvironment.

Conclusion: Immunotherapies using anti-PD-1/PD-L1 strategies are a promising treatment options for patients with multiple myeloma.

Keywords:

Coinhibitory molecule PD-1, microenvironment, multiple myeloma, T-cell-mediated apoptosis, PD-L1, immunosuppressive.

Affiliation:

Multiple Myeloma Program, Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, UTAH, Multiple Myeloma Program, Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, UTAH, Multiple Myeloma Program, Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, UTAH, Department of Stem Cell Transplantatio, University Medical Center Hamburg-Eppendorf, Martinistrabe 52, 20246 Hamburg

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