Ohta Tetsuo, Elnemr Ayman, Kitagawa Hirohisa, Kayahara Masato, Takamura Hiroyuki, Fujimura Takashi, Nishimura Gen-Ichi, Shimizu Koichi, Yi Shuang-Qin, Miwa Koichi
Department of Surgical Oncology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0934, Japan.
Oncol Rep. 2004 Oct;12(4):749-54.
Tumor cells escape immunologic rejection through diverse mechanisms. Fas and its ligand represent one such mechanism. Recently we reported that pancreatic cancer cell lines express Fas-ligand and kill lymphoid cells by Fas-mediated apoptosis in vitro. This study was designed to determine whether human pancreatic tumors express Fas-ligand in vivo, as a potential mediator of counterattacking the host immune cells, and to determine if Fas-ligand expression correlates with clinicopathologic characteristics and patient survival. Fas-ligand expression in 45 primary pancreatic ductal cancers and two hepatic metastases was determined using immunohistochemistry. Apoptotic cells within the tumor were assessed by immunohistochemistry for the presence of single stranded DNA. Immunohistochemistry showed that 37 (82%) of the primary tumors and both of the hepatic metastases expressed Fas-ligand. Tumor infiltrating lymphoid cells were frequently apoptotic, but the cancer cells were rarely apoptotic. Patients with Fas-ligand-positive tumor had significantly shorter survival times than Fas-ligand-negative. A multivariate analysis indicated that Fas-ligand expression and the histologic margin status were significant prognostic factors. These results suggest that the expression of Fas-ligand in human pancreatic cancers and the induction of apoptosis in the infiltrating lymphoid cells may be required to counterattack the host cytotoxic T-lymphocytic and natural killer cellular responses.
肿瘤细胞通过多种机制逃避免疫排斥。Fas及其配体就是其中一种机制。最近我们报道，胰腺癌细胞系表达Fas配体，并在体外通过Fas介导的凋亡杀死淋巴细胞。本研究旨在确定人类胰腺肿瘤在体内是否表达Fas配体，作为反击宿主免疫细胞的潜在介质，并确定Fas配体表达是否与临床病理特征及患者生存率相关。采用免疫组织化学法测定45例原发性胰腺导管癌和2例肝转移癌中Fas配体的表达。通过免疫组织化学检测肿瘤内凋亡细胞中单链DNA的存在情况来评估凋亡细胞。免疫组织化学显示，37例（82%）原发性肿瘤及2例肝转移癌均表达Fas配体。肿瘤浸润淋巴细胞常发生凋亡，但癌细胞很少凋亡。Fas配体阳性肿瘤患者的生存时间明显短于Fas配体阴性患者。多因素分析表明，Fas配体表达和组织学切缘状态是重要的预后因素。这些结果提示，人类胰腺癌中Fas配体的表达以及浸润淋巴细胞凋亡的诱导可能是反击宿主细胞毒性T淋巴细胞和自然杀伤细胞反应所必需的。
