Potent anti-myeloma efficacy of dendritic cell therapy in combination with pomalidomide and programmed death-ligand 1 blockade in a preclinical model of multiple myeloma

树突状细胞疗法联合泊马度胺和程序性死亡配体 1 阻断剂在多发性骨髓瘤临床前模型中表现出强大的抗骨髓瘤疗效

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作者:Tan-Huy Chu #, Manh-Cuong Vo #, Hye-Seong Park, Thangaraj Jaya Lakshmi, Sung-Hoon Jung, Hyeoung-Joon Kim, Je-Jung Lee

Abstract

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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