Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue.
Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue.
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DOI：
10.1007/s00262-013-1446-2
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Robins H
中科院分区：
文献类型：
--
作者：
Sherwood AM;Emerson RO;Scherer D;Habermann N;Buck K;Staffa J;Desmarais C;Halama N;Jaeger D;Schirmacher P;Herpel E;Kloor M;Ulrich A;Schneider M;Ulrich CM;Robins H
结直肠癌（CRC）的肿瘤通常是免疫原性的，通常被t淋巴细胞浸润。然而，对这些肿瘤的适应性免疫反应的细节了解甚少。我们收集了15例结直肠癌患者的结肠肿瘤样本和邻近健康粘膜样本来研究淋巴细胞浸润这些组织。我们采用一种高通量的方法，对CRC肿瘤浸润淋巴细胞（til）的t细胞受体（TCR）序列进行详细测序，以探测t细胞克隆，并与邻近健康粘膜组织的TCR进行比较。同时，我们使用标准免疫组织化学捕获TIL计数。TIL库多样性的变化远远大于健康粘膜中t细胞克隆的变化，肿瘤中的低克隆性平均较高。然而，CRC肿瘤和健康粘膜中t细胞库的多样性平均比外周血低100倍。使用TCR序列来识别和跟踪粘膜和肿瘤样本之间的克隆，我们确定肿瘤中的免疫反应不同于邻近粘膜组织，并且共享克隆的数量不依赖于样本之间的距离。总之，这些数据表明，结直肠癌肿瘤诱导特异性适应性免疫反应，但这种反应的强度和广度在患者之间差异很大。
Tumors from colorectal cancer (CRC) are generally immunogenic and commonly infiltrated with T-lymphocytes. However, the details of the adaptive immune reaction to these tumors are poorly understood. We have accrued both colon tumor samples and adjacent healthy mucosal samples from 15 CRC patients to study lymphocytes infiltrating these tissues. We apply a method for detailed sequencing of T-cell receptor (TCR) sequences from tumor infiltrating lymphocytes (TILs) in CRC tumors at high throughput to probe T-cell clones in comparison to the TCRs from adjacent healthy mucosal tissue. In parallel, we captured TIL counts using standard immunohistochemistry. The variation in diversity of the TIL repertoire was far wider than the variation of T-cell clones in the healthy mucosa, and the oligoclonality was higher on average in the tumors. However, the diversity of the T-cell repertoire in both CRC tumors and healthy mucosa was on average 100-fold lower than in peripheral blood. Using the TCR sequences to identify and track clones between mucosal and tumor samples, we determined that the immune response in the tumor is different than in the adjacent mucosal tissue, and the number of shared clones is not dependent on distance between the samples. Together, these data imply that CRC tumors induce a specific adaptive immune response, but that this response differs widely in strength and breadth between patients.
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影响因子：
56.9
作者：
Arstila, TP;Casrouge, A;Kourilsky, P
通讯作者：
Kourilsky, P
影响因子：
--
作者：
SHANNON, CE
通讯作者：
SHANNON, CE
影响因子：
11.2
作者：
Halama, Niels;Michel, Sara;Jaeger, Dirk
通讯作者：
Jaeger, Dirk
影响因子：
2.5
作者：
CONOVER, WJ;JOHNSON, ME;JOHNSON, MM
通讯作者：
JOHNSON, MM
影响因子：
2.7
作者：
May, E;Lambert, C;Duchmann, R
通讯作者：
Duchmann, R