PMID- 35413499 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220506 IS - 1936-5233 (Print) IS - 1936-5233 (Electronic) IS - 1936-5233 (Linking) VI - 20 DP - 2022 Jun TI - Novel IL-15 dendritic cells have a potent immunomodulatory effect in immunotherapy of multiple myeloma. PG - 101413 LID - S1936-5233(22)00075-4 [pii] LID - 10.1016/j.tranon.2022.101413 [doi] LID - 101413 AB - 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. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Chu, Tan-Huy AU - Chu TH AD - BioMedical 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. FAU - Vo, Manh-Cuong AU - Vo MC AD - Institute 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 Korea. FAU - Lakshmi, Thangaraj Jaya AU - Lakshmi TJ AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Ahn, Seo-Yeon AU - Ahn SY AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Kim, Mihee AU - Kim M AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Song, Ga-Young AU - Song GY AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Yang, Deok-Hwan AU - Yang DH AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Ahn, Jae-Sook AU - Ahn JS AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Kim, Hyeoung-Joon AU - Kim HJ AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. FAU - Jung, Sung-Hoon AU - Jung SH AD - Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, South Korea. Electronic address: shglory@hanmail.net. FAU - Lee, Je-Jung AU - Lee JJ AD - BioMedical 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: drjejung@chonnam.ac.kr. LA - eng PT - Journal Article DEP - 20220409 PL - United States TA - Transl Oncol JT - Translational oncology JID - 101472619 PMC - PMC9006865 OTO - NOTNLM OT - Immunology OT - T cells OT - cytokine induced killer cells OT - multiple myeloma OT - natural killer cells COIS- The authors declare no conflicts of interest. EDAT- 2022/04/13 06:00 MHDA- 2022/04/13 06:01 PMCR- 2022/04/09 CRDT- 2022/04/12 20:11 PHST- 2022/02/07 00:00 [received] PHST- 2022/03/25 00:00 [revised] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/04/13 06:00 [pubmed] PHST- 2022/04/13 06:01 [medline] PHST- 2022/04/12 20:11 [entrez] PHST- 2022/04/09 00:00 [pmc-release] AID - S1936-5233(22)00075-4 [pii] AID - 101413 [pii] AID - 10.1016/j.tranon.2022.101413 [doi] PST - ppublish SO - Transl Oncol. 2022 Jun;20:101413. doi: 10.1016/j.tranon.2022.101413. Epub 2022 Apr 9.