Zhou Li, Niu Zhe-Yu, Liang Zhi-Yong, Zhou Wei-Xun, You Lei, Wang Meng-Yi, Yao Lu-Tian, Liao Quan, Zhao Yu-Pei
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College Beijing 100730, China.
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College Beijing 100730, China.
Am J Transl Res. 2015 Oct 15;7(10):2036-44. eCollection 2015.
Human leucocyte antigen G (HLA-G) was shown to be associated with immune suppression and unfavorable prognosis in multiple types of cancers. However, its expression in pancreatic cancer (PC) was less investigated. Particularly, its roles in PC remain unknown. The present study aimed to address the issues. Expression of HLA-G was detected by Western blot and tissue microarray-based immunohistochemical staining in 10 and 158 patients with PC, respectively. In addition, tumor infiltrating lymphocytes (TIL) labeled by CD3 staining, as a marker of host immune response, were counted. Finally, immunohistochemical HLA-G expression was linked to clinicopathologic variables, TIL number and overall survival. It was found that HLA-G was overexpressed in 4 out of 10 patients. For staining, HLA-G expression was much higher in tumor than in non-tumor tissues. Tumoral expression of HLA-G was closely associated with T stage. Intratumoral CD3-positive TIL in tumors with diffuse HLA-G expression was less than that in those with negative or local HLA-G expression, but no significant differences for stromal TIL were observed. Univariate analysis found that diffuse HLA-G expression in tumor tissues and low intratumoral CD3-positive TIL number were of predictive significance for poor overall survival of PC. Furthermore, HLA-G expression and intratumoral CD3-positive TIL number were identified, by multivariate Cox regression test, as independent prognostic factors. Our data suggest that HLA-G impairs host immune response and predicts poor prognosis in PC.
人类白细胞抗原G(HLA-G)已被证明与多种癌症的免疫抑制和不良预后相关。然而,其在胰腺癌(PC)中的表达研究较少。特别是,其在PC中的作用仍不清楚。本研究旨在解决这些问题。分别通过蛋白质免疫印迹法和基于组织芯片的免疫组化染色检测了10例和158例PC患者中HLA-G的表达。此外,计数了以CD3染色标记的肿瘤浸润淋巴细胞(TIL),作为宿主免疫反应的标志物。最后,将免疫组化HLA-G表达与临床病理变量、TIL数量和总生存期联系起来。结果发现,10例患者中有4例HLA-G过表达。就染色而言,HLA-G在肿瘤组织中的表达远高于非肿瘤组织。HLA-G的肿瘤表达与T分期密切相关。弥漫性HLA-G表达的肿瘤中瘤内CD3阳性TIL少于HLA-G阴性或局部表达的肿瘤,但基质TIL未观察到显著差异。单因素分析发现,肿瘤组织中弥漫性HLA-G表达和瘤内CD3阳性TIL数量低对PC患者总生存期差具有预测意义。此外,通过多因素Cox回归检验,HLA-G表达和瘤内CD3阳性TIL数量被确定为独立的预后因素。我们的数据表明,HLA-G损害宿主免疫反应并预测PC患者预后不良。