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通过T细胞受体测序分析胰腺癌中肿瘤浸润淋巴细胞和循环淋巴细胞库的特征

Characteristics of Tumor Infiltrating Lymphocyte and Circulating Lymphocyte Repertoires in Pancreatic Cancer by the Sequencing of T Cell Receptors.

作者信息

Bai Xueli, Zhang Qi, Wu Song, Zhang Xiaoyu, Wang Mingbang, He Fusheng, Wei Tao, Yang Jiaqi, Lou Yu, Cai Zhiming, Liang Tingbo

机构信息

Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Key Laboratory of Cancer Prevention and Intervention, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Sci Rep. 2015 Sep 2;5:13664. doi: 10.1038/srep13664.

Abstract

Pancreatic cancer has a poor prognosis and few effective treatments. The failure of treatment is partially due to the high heterogeneity of cancer cells within the tumor. T cells target and kill cancer cells by the specific recognition of cancer-associated antigens. In this study, T cells from primary tumor and blood of sixteen patients with pancreatic cancer were characterized by deep sequencing. T cells from blood of another eight healthy volunteers were also studied as controls. By analyzing the complementary determining region 3 (CDR3) gene sequence, we found no significant differences in the T cell receptor (TCR) repertoires between patients and healthy controls. Types and length of CDR3 were similar among groups. However, two clusters of patients were identified according to the degree of CDR3 overlap within tumor sample group. In addition, clonotypes with low frequencies were found in significantly higher numbers in primary pancreatic tumors compared to blood samples from patients and healthy controls. This study is the first to characterize the TCR repertoires of pancreatic cancers in both primary tumors and matched blood samples. The results imply that specific types of pancreatic cancer share potentially important immunological characteristics.

摘要

胰腺癌的预后较差,有效治疗方法也很少。治疗失败部分归因于肿瘤内癌细胞的高度异质性。T细胞通过特异性识别癌症相关抗原来靶向并杀死癌细胞。在本研究中,通过深度测序对16例胰腺癌患者原发肿瘤和血液中的T细胞进行了表征。另外8名健康志愿者血液中的T细胞也作为对照进行了研究。通过分析互补决定区3(CDR3)基因序列,我们发现患者和健康对照之间的T细胞受体(TCR)库没有显著差异。各组之间CDR3的类型和长度相似。然而,根据肿瘤样本组内CDR3重叠程度鉴定出了两组患者。此外,与患者血液样本和健康对照相比,在原发性胰腺肿瘤中发现低频克隆型的数量明显更多。本研究首次对原发性肿瘤和匹配血液样本中的胰腺癌TCR库进行了表征。结果表明特定类型的胰腺癌具有潜在重要的免疫特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a941/4556988/b2a59f30be13/srep13664-f1.jpg

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