生物
互补决定区
主要组织相容性复合体
体细胞
抗原
T细胞
表位
人类白细胞抗原
遗传学
CD8型
免疫学
癌症研究
基因
免疫系统
肽序列
作者
Bo Li,Taiwen Li,Jean Christophe Pignon,Binbin Wang,Jinzeng Wang,Sachet A. Shukla,Ruoxu Dou,Qianming Chen,F. Stephen Hodi,Toni K. Choueiri,Catherine J. Wu,Nir Hacohen,Sabina Signoretti,Jun S. Liu,X. Shirley Liu
出处
期刊:Nature Genetics
[Springer Nature]
日期:2016-05-30
卷期号:48 (7): 725-732
被引量:256
摘要
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.
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