Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma
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Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma. / Atanackovic, D; Luetkens, T; Kröger, N.
In: LEUKEMIA, Vol. 28, No. 5, 01.05.2014, p. 993-1000.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma
AU - Atanackovic, D
AU - Luetkens, T
AU - Kröger, N
PY - 2014/5/1
Y1 - 2014/5/1
N2 - The adaptive immune system is clearly capable of recognizing and attacking malignant plasma cells in patients with multiple myeloma (MM). However, MM patients evidence severe defects of humoral and cellular immunity, and it is likely that the profound immune dysregulation typical for this malignancy contributes to its eventual escape from natural immune control. One of the factors responsible for the immune dysfunction in MM might be the programmed death 1 (PD-1) protein. The physiological role of PD-1 is to guarantee T-cell homeostasis by limiting T-cell activation and proliferation. Accordingly, binding of the ligand PD-L1 to PD-1 expressed on the surface of activated T cells delivers an inhibitory signal, reducing cytokine production and proliferation. Using the same mechanism, PD-L1/PD-1 interactions have been shown in a number of animal models to confer tumor escape from immune control. Recently, clinical trials have suggested a significant therapeutic impact of PD-1/PD-L inhibition on a variety of solid tumors-for example, by the application of monoclonal antibodies. We show here that based on (1) the broad expression of PD-1 and its ligands in the microenvironment of myeloma, (2) data indicating an important role of the PD-1 pathway in the immune evasion by MM cells and (3) preclinical results providing a strong rationale for therapeutic PD-1/PD-L inhibition in this malignancy, MM may be very well suited for immunotherapy, for example, a monoclonal antibody, targeting PD-1 and/or its ligands.
AB - The adaptive immune system is clearly capable of recognizing and attacking malignant plasma cells in patients with multiple myeloma (MM). However, MM patients evidence severe defects of humoral and cellular immunity, and it is likely that the profound immune dysregulation typical for this malignancy contributes to its eventual escape from natural immune control. One of the factors responsible for the immune dysfunction in MM might be the programmed death 1 (PD-1) protein. The physiological role of PD-1 is to guarantee T-cell homeostasis by limiting T-cell activation and proliferation. Accordingly, binding of the ligand PD-L1 to PD-1 expressed on the surface of activated T cells delivers an inhibitory signal, reducing cytokine production and proliferation. Using the same mechanism, PD-L1/PD-1 interactions have been shown in a number of animal models to confer tumor escape from immune control. Recently, clinical trials have suggested a significant therapeutic impact of PD-1/PD-L inhibition on a variety of solid tumors-for example, by the application of monoclonal antibodies. We show here that based on (1) the broad expression of PD-1 and its ligands in the microenvironment of myeloma, (2) data indicating an important role of the PD-1 pathway in the immune evasion by MM cells and (3) preclinical results providing a strong rationale for therapeutic PD-1/PD-L inhibition in this malignancy, MM may be very well suited for immunotherapy, for example, a monoclonal antibody, targeting PD-1 and/or its ligands.
KW - Animals
KW - Humans
KW - Immunotherapy
KW - Lymphocyte Activation
KW - Multiple Myeloma
KW - Programmed Cell Death 1 Receptor
KW - Stem Cell Transplantation
KW - T-Lymphocytes
U2 - 10.1038/leu.2013.310
DO - 10.1038/leu.2013.310
M3 - SCORING: Journal article
C2 - 24153012
VL - 28
SP - 993
EP - 1000
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 5
ER -