Date Ippei, Koya Terutsugu, Sakamoto Takuya, Togi Misa, Kawaguchi Haruhiko, Watanabe Asuka, Kato Tomohisa, Shimodaira Shigetaka
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan.
Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan.
Vaccines (Basel). 2020 Dec 24;9(1):10. doi: 10.3390/vaccines9010010.
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.
鉴于免疫检查点抑制剂的最新进展，基于树突状细胞（DC）的疫苗接种所提供的癌症免疫疗法备受关注。尽管已经进行了许多研究来确定DC疫苗对抗癌症的效力，但临床结果尚未达到最佳，仍需进一步改进。在本研究中，我们评估了人血小板裂解物（HPL）产生干扰素-α诱导的DC（IFN-DC）的潜在能力。在HPL存在的情况下，IFN-DC（HPL-IFN-DC）表现出高活力、高产量和高纯度。此外，与无HPL产生的IFN-DC相比，HPL-IFN-DC的CD14、CD56和CCR7表达增加；HPL-IFN-DC诱导的抗原特异性细胞毒性T淋巴细胞（CTL）数量比IFN-DC多得多，这是通过用T细胞识别的人白细胞抗原（HLA）限制性黑色素瘤抗原1（MART-1）肽评估的。此外，HPL-IFN-DC的内吞和蛋白水解活性增加。HPL-IFN-DC中白细胞介素（IL）-6、IL-10和肿瘤坏死因子（TNF）-α的细胞因子产生也升高，这可能解释了CTL、内吞和蛋白水解活性的增强。我们的研究结果表明，体外产生的HPL-IFN-DC是一种新型的单核细胞来源的DC，具有高内吞和蛋白水解活性，从而突出了基于DC的免疫疗法的独特策略。
