Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 1, Pages 31-45Publisher
SPRINGER
DOI: 10.1007/s00262-020-02654-0
Keywords
Myeloma; Dendritic cells; Pomalidomide; Anti-PD-L1; Combination therapy; Cancer immunotherapy
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Funding
- National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology (MEST), Republic of Korea [2018R1A5A2024181, NRF-2018R1C1B5041536, NRF-2020R1A2C2010098]
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The study demonstrates that combining DC vaccine, pomalidomide, and PD-L1 blockade can inhibit tumor growth in a multiple myeloma mouse model. It also enhances the proportions of immune effector cells in the spleen and tumor microenvironment, as well as improves the functional activities of cytotoxic T lymphocytes and NK cells in the spleen.
Dendritic cell (DC)-based vaccines are recognized as a promising immunotherapeutic strategy against cancer; however, the efficacy of immunotherapy with DCs is controlled via immune checkpoints, such as programmed death-ligand 1 (PD-L1). PD-L1 expressed on DC and tumor cells binds to programmed death-1 (PD-1) receptors on the activated T cells, which leads to the inhibition of cytotoxic T cells. Blocking of PD-L1 on DC may lead to improve the efficacy of DC therapy for cancer. Here we demonstrated that DC vaccination in combination with pomalidomide and programmed death-ligand 1 (PD-L1) blockade inhibited tumor growth of a multiple myeloma (MM) mouse model. DCs + pomalidomide with dexamethasone + PD-L1 blockade significantly inhibited immune immunosuppressive factors and promoted proportions of immune effector cells in the spleen and tumor microenvironment. Additionally, functional activities of cytotoxic T lymphocytes and NK cells in spleen were enhanced by DCs + pomalidomide with dexamethasone + PD-L1 blockade. Taken together, this study identifies a potential new therapeutic approach for the treatment of MM. These results also provide a foundation for the future development of immunotherapeutic modalities to inhibit tumor growth and restore immune function in MM.
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