Department of Surgery, Tohoku University Hospital, Sendai, Japan.
Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Virchows Arch. 2020 Dec;477(6):825-834. doi: 10.1007/s00428-020-02854-0. Epub 2020 Jun 12.
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.
免疫微环境在癌症的发生和发展中起着关键作用。因此,我们研究了食管腺癌(EAC)和相邻 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 87 例接受手术切除或内镜黏膜下剥离术的 EAC 患者。在 EAC 和相邻 BE(N=87)以及无 EAC 的 BE(N=13)中免疫定位了 CD3、CD8、Foxp3、p53 和 Ki-67。与无 EAC 的 BE 相比,EAC 相邻 BE 中的 CD3+固有层淋巴细胞(LPL)数量更高。BE 中丰富的 Foxp3+LPL 与异型增生和 BE 腺细胞中 Ki-67 标记指数(LI)增加有关,且与异常 p53 表达有关。相邻 BE 中丰富的 CD8+LPL 与 EAC 患者的预后较差有关(P=0.019)。本研究结果首次揭示了 EAC 相邻 BE 的组织免疫微环境对癌症发生和 EAC 患者最终临床结局的潜在影响。T 细胞浸润可能在促进 BE 中的异型增生-腺癌序列中发挥关键作用。Foxp3+T 细胞数量在癌变的早期增加,有助于识别存在异型增生和高增殖细胞的患者。CD8+T 细胞可反映相邻组织微环境中不利的炎症反应,并有助于预测 EAC 患者的预后不良。