PMID- 33374342 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210218 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 9 IP - 1 DP - 2020 Dec 24 TI - Interferon-alpha-Induced Dendritic Cells Generated with Human Platelet Lysate Exhibit Elevated Antigen Presenting Ability to Cytotoxic T Lymphocytes. LID - 10.3390/vaccines9010010 [doi] LID - 10 AB - Given the recent advancements of immune checkpoint inhibitors, there is considerable interest in cancer immunotherapy provided through dendritic cell (DC)-based vaccination. Although many studies have been conducted to determine the potency of DC vaccines against cancer, the clinical outcomes are not yet optimal, and further improvement is necessary. In this study, we evaluated the potential ability of human platelet lysate (HPL) to produce interferon-alpha-induced DCs (IFN-DCs). In the presence of HPL, IFN-DCs (HPL-IFN-DCs) displayed high viability, yield, and purity. Furthermore, HPL-IFN-DCs displayed increased CD14, CD56, and CCR7 expressions compared with IFN-DCs produced without HPL; HPL-IFN-DCs induced an extremely higher number of antigen-specific cytotoxic T lymphocytes (CTLs) than IFN-DCs, which was evaluated with a human leukocyte antigen (HLA)-restricted melanoma antigen recognized by T cells 1 (MART-1) peptide. Additionally, the endocytic and proteolytic activities of HPL-IFN-DCs were increased. Cytokine production of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha was also elevated in HPL-IFN-DCs, which may account for the enhanced CTL, endocytic, and proteolytic activities. Our findings suggest that ex-vivo-generated HPL-IFN-DCs are a novel monocyte-derived type of DC with high endocytic and proteolytic activities, thus highlighting a unique strategy for DC-based immunotherapies. FAU - Date, Ippei AU - Date I AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. FAU - Koya, Terutsugu AU - Koya T AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan. FAU - Sakamoto, Takuya AU - Sakamoto T AUID- ORCID: 0000-0003-2519-4510 AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan. FAU - Togi, Misa AU - Togi M AUID- ORCID: 0000-0002-7424-4548 AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan. FAU - Kawaguchi, Haruhiko AU - Kawaguchi H AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. FAU - Watanabe, Asuka AU - Watanabe A AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. FAU - Kato, Tomohisa Jr AU - Kato T Jr AD - Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. FAU - Shimodaira, Shigetaka AU - Shimodaira S AUID- ORCID: 0000-0002-6612-6912 AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan. LA - eng PT - Journal Article DEP - 20201224 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC7823331 OTO - NOTNLM OT - cytotoxic T lymphocyte OT - dendritic cells OT - endocytosis OT - human platelet lysate OT - immunotherapy OT - proteolytic activity OT - tumor-associated antigens OT - vaccine COIS- All authors, except for S.S., T.K., T.S., and M.T., declare no conflicts of interest. S.S., T.K., T.S., and M.T. evaluated DCO-K serum-free medium (Nissui Pharmaceutical Co., Ltd.) for the DC culture. Kanazawa Medical University concludes a collaborative investigation contract with Nissui Pharmaceutical Co., Ltd. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/12/31 06:00 MHDA- 2020/12/31 06:01 PMCR- 2020/12/24 CRDT- 2020/12/30 01:01 PHST- 2020/11/25 00:00 [received] PHST- 2020/12/21 00:00 [revised] PHST- 2020/12/21 00:00 [accepted] PHST- 2020/12/30 01:01 [entrez] PHST- 2020/12/31 06:00 [pubmed] PHST- 2020/12/31 06:01 [medline] PHST- 2020/12/24 00:00 [pmc-release] AID - vaccines9010010 [pii] AID - vaccines-09-00010 [pii] AID - 10.3390/vaccines9010010 [doi] PST - epublish SO - Vaccines (Basel). 2020 Dec 24;9(1):10. doi: 10.3390/vaccines9010010.