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

Cancer Immunol Immunother. 2021 Jan;70(1):31-45. doi: 10.1007/s00262-020-02654-0. Epub 2020 Jul 4.

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.

Keywords: Anti-PD-L1; Cancer immunotherapy; Combination therapy; Dendritic cells; Myeloma; Pomalidomide.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Cell Proliferation / drug effects
  • Cell- and Tissue-Based Therapy / methods
  • Cells, Cultured
  • Chemotherapy, Adjuvant / methods
  • Dendritic Cells / immunology*
  • Drug Evaluation, Preclinical / methods
  • Female
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immunosuppressive Agents / pharmacology
  • Immunotherapy / methods
  • Mice
  • Mice, Inbred BALB C
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacology
  • Vaccination / methods

Substances

  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Immune Checkpoint Inhibitors
  • Immunosuppressive Agents
  • Thalidomide
  • pomalidomide