Landscape of tumor-infiltrating T cell repertoire of human cancers
Landscape of tumor-infiltrating T cell repertoire of human cancers
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DOI：
10.1038/ng.3581
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发表时间：
2016-07-01
期刊：
影响因子：
30.8
通讯作者：
Liu, X. Shirley
中科院分区：
文献类型：
--
作者：
Li, Bo;Li, Taiwen;Liu, X. Shirley
我们开发了一种计算方法来推断29种癌症类型的9,142个RNA-SEQ样本中肿瘤浸润性T细胞的互补决定区3(CDR3)序列。我们鉴定了60多万个CDR3序列，其中15%是全长的。CDR3序列长度分布和氨基酸保守性，以及可变的基因使用，在许多肿瘤中渗透T细胞，除了脑和肾癌，类似于来自健康捐赠者的外周血细胞。我们观察到T细胞多样性和肿瘤突变负荷之间有很强的相关性，我们预测SPAG5和TSSK6在多种癌症中可能是免疫原性癌症/睾丸抗原。最后，根据它们与CDR3序列的共现情况，我们鉴定了三个潜在的免疫原性体细胞突变。其中一个是编码P.Phe300Val的PRAMEF4突变，它被预测导致多肽与MHC I类和II类分子强烈结合，其携带者中有匹配的HLA型。我们的分析有可能同时识别免疫原性新抗原和肿瘤反应性T细胞克隆型。
We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified three potential immunogenic somatic mutations on the basis of their co-occurrence with CDR3 sequences. One of them, a PRAMEF4 mutation encoding p. Phe300Val, was predicted to result in peptide binding strongly to both MHC class I and class II molecules, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes.