Статья

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

Tan-Huy ChuBioMedical Sciences Graduate Program, Chonnam National University, South Korea; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaManh-Cuong VoInstitute of Research and Development, Duy Tan University, Danang, Vietnam; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaJaya Lakshmi ThangarajDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaSeo-Yeon AhnDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaMihee KimDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaGa‐Young SongDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaDeok‐Hwan YangDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaJae‐Sook AhnDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaHyeoung‐Joon KimDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South KoreaSung‐Hoon JungDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. Electronic address: [email protected]Je‐Jung LeeBioMedical Sciences Graduate Program, Chonnam National University, South Korea; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. Electronic address: [email protected]

2022en

ABI

Аннотация

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-γ was significantly higher compared to conventional mDCs. IL-15 mDCs (6 days) showed superior polarization of naïve 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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Идентификаторы

DOI: 10.1016/j.tranon.2022.101413

Цитирования и источники

Цитирований: 2Использованных источников: 0

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