Narita Miwako, Kanda Tatsuo, Abe Takashi, Uchiyama Takayoshi, Iwafuchi Minami, Zheng Zhiyin, Liu Aichun, Kaifu Tsutomu, Kosugi Shinichi, Minagawa Masahiro, Itoh Kyogo, Takahashi Masuhiro
Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata 951‑8518, Japan.
Department of Surgery, School of Medicine, Niigata University, Niigata 951‑8520, Japan.
Int J Oncol. 2015 Apr;46(4):1699-709. doi: 10.3892/ijo.2015.2846. Epub 2015 Jan 23.
Patients with advanced stage of squamous cell carcinoma of esophagus have a poor prognosis with a lethal outcome. In order to explore the feasibility and effectiveness of dendritic cell (DC)-based immunotherapy for squamous cell carcinoma of esophagus, we performed a phase I/II clinical trial of monocyte-derived dendritic cells (moDCs) pulsed with SART1 peptide in seven patients with advanced stage of this disease. Although the feasibility of this therapy was definite, the effectiveness was not clearly confirmed in advanced stage of squamous cell carcinoma of esophagus. However, in vitro study revealed that moDCs generated for this therapy possessed a potent ability of inducing SART1 peptide-specific cytotoxic T lymphocytes (CTLs). In addition, these moDCs were demonstrated to be able to produce exosomes with an antigen presenting ability for inducing SART1 peptide-specific CTLs. ELISPOT assay using cryopreserved patient's lymphocytes demonstrated that IFN-γ ELISPOTs were increased after four times of SART1 peptide-pulsed moDC vaccinations compared with before the vaccination in a patient. The present study demonstrated that moDCs prepared from advanced stage of squamous cell carcinoma of esophagus possess a good immune function and in vivo immune responses (detected by ELISPOT assay) were evoked by the infusion of these moDCs. These findings suggest that DC-based immunotherapy could be one of the modalities applicable for squamous cell carcinoma of esophagus.
晚期食管鳞状细胞癌患者预后较差，最终会导致死亡。为了探索基于树突状细胞（DC）的免疫疗法对食管鳞状细胞癌的可行性和有效性，我们对7例晚期食管鳞状细胞癌患者进行了一项I/II期临床试验，用SART1肽脉冲单核细胞来源的树突状细胞（moDCs）。虽然这种疗法的可行性是确定的，但在晚期食管鳞状细胞癌中其有效性尚未得到明确证实。然而，体外研究表明，为此疗法生成的moDCs具有诱导SART1肽特异性细胞毒性T淋巴细胞（CTLs）的强大能力。此外，这些moDCs被证明能够产生具有抗原呈递能力的外泌体，以诱导SART1肽特异性CTLs。使用冷冻保存的患者淋巴细胞进行的ELISPOT分析表明，与一名患者接种疫苗前相比，在进行4次SART1肽脉冲moDC疫苗接种后，IFN-γ ELISPOTs增加。本研究表明，从晚期食管鳞状细胞癌制备的moDCs具有良好的免疫功能，并且通过输注这些moDCs可引发体内免疫反应（通过ELISPOT分析检测）。这些发现表明，基于DC的免疫疗法可能是适用于食管鳞状细胞癌的治疗方式之一。
