Nishimura Junya, Deguchi Sota, Tanaka Hiroaki, Yamakoshi Yoshihito, Yoshii Mami, Tamura Tatsuro, Toyokawa Takahiro, Lee Shigeru, Muguruma Kazuya, Ohira Masaichi
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
In Vivo. 2021 Mar-Apr;35(2):743-752. doi: 10.21873/invivo.12315.
BACKGROUND/AIM: Neoadjuvant chemotherapy (NAC) using 5-FU (5-fluorouracil)/CDDP (cisplatin) is a standard therapy for stage II/III thoracic esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to investigate whether 5-FU/CDDP could induce immunogenic cell death in ESCC cell lines.
Tumor samples for immunohistochemistry were obtained from 50 patients (mean age=63.1 years) with pathological stage 0-IVa ESCC who underwent NAC followed by surgery. Cell lines T.T and KYSE30 were used for the in vitro experiments.
The concentrations of HMGB1 were elevated in the cell line supernatants treated with 5-FU/CDDP. 5-FU/CDDP treated dendritic cells (DCs) showed a mature phenotype, and enhanced T cell proliferation capacity. In addition, mature DCs were observed in surgical specimens with a histological response after treatment with 5-FU/CDDP chemotherapy.
5-FU/CDDP could induce immunogenic cell death in the tumor microenvironment of ESCC.
背景/目的:在日本,使用5-氟尿嘧啶(5-FU)/顺铂(CDDP)的新辅助化疗(NAC)是II/III期胸段食管鳞状细胞癌(ESCC)的标准治疗方法。本研究的目的是调查5-FU/CDDP是否能在ESCC细胞系中诱导免疫原性细胞死亡。
免疫组织化学所用的肿瘤样本取自50例(平均年龄=63.1岁)病理分期为0-IVa期的ESCC患者,这些患者接受了NAC然后进行手术。细胞系T.T和KYSE30用于体外实验。
用5-FU/CDDP处理的细胞系上清液中高迁移率族蛋白B1(HMGB1)的浓度升高。用5-FU/CDDP处理的树突状细胞(DCs)表现出成熟的表型,并增强了T细胞增殖能力。此外,在用5-FU/CDDP化疗后有组织学反应的手术标本中观察到成熟的DCs。
5-FU/CDDP可在ESCC的肿瘤微环境中诱导免疫原性细胞死亡。