T cell receptor β-chain repertoire analysis of tumor-infiltrating lymphocytes in pancreatic cancer
T cell receptor β-chain repertoire analysis of tumor-infiltrating lymphocytes in pancreatic cancer
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DOI：
10.1111/cas.13877
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发表时间：
2019-01-01
期刊：
影响因子：
5.7
通讯作者：
Hao, Chunyi
中科院分区：
文献类型：
--
作者：
Cui, Can;Tian, Xiuyun;Hao, Chunyi
由于缺乏明显的症状和有效的治疗方法，胰腺癌是致命的。免疫疗法可能为胰腺癌等恶性肿瘤提供有希望的治疗选择。肿瘤间充质中的肿瘤浸润淋巴细胞（TIL）可以识别肿瘤细胞表面的肽抗原。本研究旨在测试肿瘤T细胞受体（TCR）β库与外周血之间的关系，并研究胰腺癌中TCRβ库的肿瘤内空间异质性。据我们所知，这是第一项评估胰腺癌空间范围内 TIL 中 TCR β 库克隆组成的研究。在这项研究中，我们研究了 5 名被诊断患有原发性胰腺癌的患者。使用超深度测序来评估 TCR β 链 (TCR beta) 基因的重排。 CD3、CD4、CD8和HLA I类的HE染色和免疫组化用于宏观显示组织病理学和免疫状况。 TIL 谱库显示，同一肿瘤的不同区域之间的谱库重叠数量大于外周血之间的谱库重叠数量，这表明胰腺癌中的 T 细胞克隆可能与外周血中的 T 细胞克隆有很大不同。相比之下，单个肿瘤组织的不同区域之间的肿瘤内 TCR β 库在空间上是均匀的。基于这些结果，我们推测胰腺癌中的细胞适应性免疫反应在空间上是同质的。这可能为治疗胰腺癌患者的免疫疗法铺平道路。
Pancreatic cancer is lethal due to lack of perceptible symptoms and effective treatment methods. Immunotherapy may provide promising therapeutic choices for malignant tumors like pancreatic cancer. Tumor-infiltrating lymphocytes (TIL) in tumor mesenchyme could recognize peptide antigens presented on the surface of tumor cells. The present study aimed to test the relationship between the T cell receptor (TCR) beta repertoire of the tumor and peripheral blood, and also to investigate the intra-tumor spatial heterogeneity of the TCR beta repertoire in pancreatic cancer. To the best of our knowledge, this is the first study to evaluate the clonal composition of TCR beta repertoire in TIL across the spatial extent of pancreatic cancer. In this study, we studied 5 patients who were diagnosed with primary pancreatic cancer. Ultra-deep sequencing was used to assess the rearrangement of the TCR beta-chain (TCR beta) gene. HE staining and immunohistochemistry of CD3, CD4, CD8 and HLA class I were used to show histopathology and immune conditions macroscopically. TIL repertoire showed that different regions of the same tumor showed a greater number of repertoire overlaps between each other than between peripheral blood, which suggested that T cell clones in pancreatic cancer might be quite different from those in peripheral blood. In contrast, intra-tumoral TCR beta repertoires were spatially homogeneous between different regions of a single tumor tissue. Based on these results, we speculated that the cellular adaptive immune response in pancreatic cancer was spatially homogeneous; this may pave the way for immunotherapy for the treatment of pancreatic cancer patients.