Interferon-α-Induced Dendritic Cells Generated with Human Platelet Lysate Exhibit Elevated Antigen Presenting Ability to Cytotoxic T Lymphocytes

Ippei Date; Terutsugu Koya; Takuya Sakamoto; Misa Togi; Haruhiko Kawaguchi; Asuka Watanabe; Tomohisa Kato Jr; Shigetaka Shimodaira

doi:10.3390/vaccines9010010

Interferon-α-Induced Dendritic Cells Generated with Human Platelet Lysate Exhibit Elevated Antigen Presenting Ability to Cytotoxic T Lymphocytes

Vaccines (Basel). 2020 Dec 24;9(1):10. doi: 10.3390/vaccines9010010.

Authors

Ippei Date¹, Terutsugu Koya^{1

2}, Takuya Sakamoto^{1

2}, Misa Togi^{1

2}, Haruhiko Kawaguchi¹, Asuka Watanabe¹, Tomohisa Kato Jr³, Shigetaka Shimodaira^{1

2}

Affiliations

¹ Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan.
² Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan.
³ Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan.

Abstract

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-α-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)-α 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.

Keywords: cytotoxic T lymphocyte; dendritic cells; endocytosis; human platelet lysate; immunotherapy; proteolytic activity; tumor-associated antigens; vaccine.