Abstract A66: Analysis of dendritic cell derived exosomes that suppressed tumor growth

M. Takanashi, K. Sudo, Shinobu Ueda, Shin-ichiro Ohno, M. Kuroda
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Abstract

Immunotherapy is expected as the fourth cancer therapy subsequently to the three pillars of cancer treatment which are surgery, radiation, and chemotherapy. Cancer immunotherapy enhances existing antitumor responses and includes the use of antibodies, lymphocytes and cytokines. Dendritic cells (DCs)-based immunotherapy is one of the cancer immunotherapies. Because DCs play a key role for immune reactions to activate T cells against cancer cells by cancer antigen presentation at cellular membrane, DCs have been used in clinical trials as cellular mediators for therapeutic vaccination of patients with cancer. The cells such as DCs and cancer cells secrete exosomes which are nano-sized extracellular microvesicles. It has reported that the exosomes released from peptide-vaccinated DCs are responsible for the persistence of antigen presentation. On the other hands, cancer cells derived exosomes play an immunosuppressive. So, we considered that whether DCs-derived exosomes could induce suppress cancer cells and more effective response of immune system against cancer with control for the cancer cells-derived exosomes. Luciferase gene transfferd-3LL cells (murine lung cancer cell line derived C57BL/6) were injected to C57BL/6J mice by intraperitoneal administration. And then, DCs, DCs-exosomes or 3LL-exosmes were weekly administrated to lung cancer bearing mice. The exosomes derived from DCs decreased lung cancer cell growth, on the other hand, lung cancer derived-exosomes increased in compared with DCs, DCs-exosomes and non-treated. For cancer immunotherapy, DC-exosomes and controlled cancer-exosomes play important roles. Currently, we are going on analyze immunosuppressive molecules possessing cancer cell-derived exosomes, and immune activation molecules in DCs-exosomes. Citation Format: Masakatsu Takanashi, Katsuko Sudo, Shinobu Ueda, Shinichiro Ohno, Masahiko Kuroda. Analysis of dendritic cell derived exosomes that suppressed tumor growth [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A66.
A66:树突状细胞来源的外泌体抑制肿瘤生长的分析
免疫治疗有望成为继手术、放射、化疗后的第四大癌症治疗方法。癌症免疫治疗增强了现有的抗肿瘤反应,包括使用抗体、淋巴细胞和细胞因子。基于树突状细胞的免疫治疗是肿瘤免疫治疗的一种。由于树突状细胞在免疫反应中发挥关键作用,通过细胞膜上的癌症抗原呈递激活T细胞对抗癌细胞,因此树突状细胞已在临床试验中用作癌症患者治疗性疫苗接种的细胞介质。细胞如dc和癌细胞分泌外泌体,它们是纳米级的细胞外微泡。据报道,从肽疫苗dc释放的外泌体负责抗原呈递的持久性。另一方面,癌细胞衍生的外泌体发挥免疫抑制作用。因此,我们考虑dcs来源的外泌体是否可以通过控制癌细胞来源的外泌体诱导抑制癌细胞和更有效的免疫系统对癌症的反应。将荧光素酶基因转移3ll细胞(来源于小鼠肺癌细胞系C57BL/6)腹腔注射至C57BL/6J小鼠。然后每周给肺癌小鼠注射dc、dc -外泌体或3ll -外泌体。dc来源的外泌体降低了肺癌细胞的生长,另一方面,肺癌来源的外泌体与dc, dc来源的外泌体和未处理的相比增加。在癌症免疫治疗中,dc -外泌体和受控癌外泌体发挥着重要作用。目前,我们正在分析癌细胞源性外泌体的免疫抑制分子和dc -外泌体的免疫激活分子。引文格式:高桥正松、须藤胜子、上田伸信、大野伸一郎、黑田正彦。抑制肿瘤生长的树突状细胞来源外泌体分析[摘要]。摘自:AACR肿瘤免疫学和免疫治疗特别会议论文集;2017年10月1-4日;波士顿,MA。费城(PA): AACR;癌症免疫,2018;6(9增刊):摘要nr A66。
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