免疫检查点蛋白质PD-1和TIM-3在肝组织中高度表达，并且与其

StephenW

Medicine (Baltimore). 2016 Dec;95(52):e5749. doi: 10.1097/MD.0000000000005749.
Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma.Li Z1, Li N, Li F, Zhou Z, Sang J, Chen Y, Han Q, Lv Y, Liu Z.
Author information

• 1aDepartment of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University bDepartment of Infectious Diseases, Yanan University Affiliated Hospital, Yanan cDepartment of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University dInstitute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi' an, Shaanxi, China.
  

AbstractImmune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis.PD-1 and TIM-3 expression in liver tissues were examined by immunohistochemistry and the genotypes of PD1 rs10204525 and TIM3 rs10053538 polymorphisms were determined using genomic DNA extracted from peripheral blood as template.Both PD-1 and TIM-3 expressions in liver infiltrating lymphocytes of HCC tumor tissues were significantly higher than those in tumor adjacent tissues or cirrhotic tissues. The elevated PD-1 and TIM-3 expressions were significantly associated with higher tumor grades. The levels between PD-1 and TIM-3 expression in tumor tissues and tumor adjacent tissues had a significant positive intercorrelation. The expressions of PD-1 and TIM-3 in tumor tissues, tumor adjacent tissues, and cirrhotic tissues were significantly associated with PD1 and TIM3 polymorphisms, with genotype AA of PD1 rs10204525 and genotypes GT+TT of TIM3 rs10053538 being associated with significantly increased PD-1 and TIM-3 expression, respectively.These findings support the potential to improve the efficiency of immune checkpoint-targeted therapy and reduce resistance to the therapy by blocking both PD-1 and TIM-3 and suggest the potential to apply the genotype determination of PD1 rs10204525 and TIM3 rs10053538 as biomarkers of immune checkpoint-directed therapies.


PMID:28033288DOI:10.1097/MD.0000000000005749

StephenW

医学（巴尔的摩）。 2016 Dec; 95（52）：e5749。 doi：10.1097 / MD.0000000000005749。
免疫检查点蛋白质PD-1和TIM-3在肝组织中高度表达，并且与其在HBV相关的肝细胞癌患者中的基因多态性相关。
Li Z1，Li N，Li F，Zhou Z，Sang J，Chen Y，Han Q，Lv Y，Liu Z。
作者信息

    1西安交通大学附属第一医院传染病科，西安延安大学附属医院传染病科，西安交通大学附属第一医院肝胆外科住院医院西安高级外科技术与工程研究所交通大学，西安，陕西，中国。

抽象

免疫检查点蛋白质程序性死亡-1（PD-1）和T细胞免疫球蛋白结构域和粘蛋白域包含分子-3（TIM-3）表达和他们的基因多态性已分别显示与乙型肝炎病毒（HBV）感染和肝细胞癌（HCC）。这项研究同时检查了肝组织和PD1和TIM3多态性中的PD-1和TIM-3表达，并分析了171例HBV相关肝癌和34例HBV相关性肝硬化PD-1和TIM-3表达的相关性通过免疫组织化学方法检测肝组织中PD1 rs10204525和TIM3 rs10053538多态性的基因型，结果显示，肝癌浸润淋巴细胞中PD-1和TIM-3的表达明显高于肝癌组织在肿瘤邻近组织或肝硬化组织。升高的PD-1和TIM-3表达与较高的肿瘤等级显着相关。肿瘤组织和肿瘤邻近组织中PD-1和TIM-3表达之间的水平具有显着的正相互关系。肿瘤组织，肿瘤相邻组织和肝硬化组织中PD-1和TIM-3的表达与PD1和TIM3多态性显着相关，其中PD1 rs10204525的基因型AA和TIM3 rs10053538的基因型GT + TT与显着增加的PD相关-1和TIM-3表达。这些发现支持通过阻断PD-1和TIM-3两者来提高免疫检查点靶向治疗的效率和减少对治疗的抗性的潜力，并且表明可能应用基因型测定的PD1 rs10204525和TIM3 rs10053538作为免疫检查点定向治疗的生物标志物。

PMID：
    28033288
DOI：
    10.1097 / MD.0000000000005749

MP4

西安交通大学