4.5 Article

Novel IL-15 dendritic cells have a potent immunomodulatory effect in immunotherapy of multiple myeloma

Journal

TRANSLATIONAL ONCOLOGY
Volume 20, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2022.101413

Keywords

Immunology; T cells; cytokine induced killer cells; natural killer cells; multiple myeloma

Categories

Funding

  1. National Research Foundation of Korea (NRF) - Korea government [NRF-2020R1A5A2031185, NRF-2020R1A2C2010098]
  2. Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIT) [NRF-2020M3A9G3080330]

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The study suggests that novel multipotent mDCs generated by the addition of IL-15 exhibit outstanding activation of T cells, CIK cells, and NK cells, which may facilitate cellular immunotherapy for cancer patients by inducing strong cytotoxicity against myeloma cells.
Dendritic cells (DCs) are the most potent antigen-presenting cells, and have thus been used in clinical cancer vaccines. However, the effects of DC vaccines are still limited, leading researchers to explore novel ways to make them effective. In this study, we investigated whether human monocyte-derived DCs generated via the addition of interleukin 15 (IL-15) had a higher capacity to induce antigen-specific T cells compared to conventional DCs. We isolated CD14+ monocytes from peripheral blood from multiple myeloma (MM) patients, and induced immature DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 in the presence or absence of IL-15 for 4-6 days. Then we generated mature DCs (mDCs) with lipopolysaccharide for another 2 days [IL-15 mDCs (6 days), IL-15 mDCs (8 days), and conventional mDCs (8 days)]. IL-15 mDCs (6 days) showed higher expression of MHC I and II, CD40, CD86, and CCR7, and the secretion of IFN-gamma was significantly higher compared to conventional mDCs. IL-15 mDCs (6 days) showed superior polarization of naive T cells toward Th1 cells and a higher proportion of activated T cells, cytokine-induced killer (CIK) cells, and natural killer (NK) cells for inducing strong cytotoxicity against myeloma cells, and lower proportion of regulatory T cells compared to conventional mDCs. These data imply that novel multipotent mDCs generated by the addition of IL-15, which can be cultivated in 6 days, resulted in outstanding activation of T cells, CIK cells and NK cells, and may facilitate cellular immunotherapy for cancer patients.

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