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Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.
Virchows Archiv ( IF 3.4 ) Pub Date : 2020-06-12 , DOI: 10.1007/s00428-020-02854-0
Yusuke Gokon 1, 2 , Fumiyoshi Fujishima 2 , Yusuke Taniyama 1 , Hirotaka Ishida 1 , Taku Yamagata 3 , Takashi Sawai 4 , Miwa Uzuki 5 , Hirofumi Ichikawa 6 , Yuko Itakura 7 , Kazutomi Takahashi 8 , Nobuhisa Yajima 9 , Motohisa Hagiwara 10 , Akiko Nishida 11 , Yohei Ozawa 12 , Tsutomu Sakuma 13 , Rikiya Kanba 14 , Kazuhiro Sakamoto 15 , Masashi Zuguchi 16 , Masahiro Saito 17 , Takashi Kamei 1 , Hironobu Sasano 2
Affiliation  

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett’s esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia–adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.



中文翻译:

邻近食管腺癌的Barrett食道的免疫微环境:邻近黏膜可能对癌症发展和进展的影响。

免疫微环境在癌症的发展和进程中起着举足轻重的作用。因此,我们研究了食管腺癌(EAC)和邻近的Barrett食管(BE)中免疫细胞的状态及其与患者临床病程的关系。我们纳入了接受外科手术切除或内镜下黏膜下剥离的87例EAC患者。CD3,CD8,Foxp3,p53和Ki-67免疫定位在EAC和相邻的BE(N  = 87)和没有EAC的BE(N = 13)。与没有EAC的BE相比,与EAC相邻的BE表现出更高的CD3 +固有层淋巴细胞(LPL)数量。BE中大量的Foxp3 + LPL与发育异常和BE腺细胞中Ki-67标记指数(LI)升高有关,并倾向于与异常的p53表达相关。相邻BE中大量CD8 + LPL与EAC患者的预后差有关(P = 0.019)。我们的研究结果首先揭示了与EAC相邻的BE的组织免疫微环境对EAC患者的癌症发展和最终临床结果的潜在影响。T细胞浸润在促进BE的异型增生-腺癌序列中可能起关键作用。在癌变的早期阶段,Foxp3 + T细胞的数量增加,并且可以帮助识别携带发育异常和高度增殖细胞的患者。CD8 + T细胞可能反映邻近组织微环境中不利的炎症反应,并有助于预测EAC患者的预后。

更新日期:2020-06-12
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