Landscape of tumor-infiltrating T cell repertoire of human cancers

被引：241

作者：

Li, Bo ^{[1
,2
]}

Li, Taiwen ^{[1
,3
]}

Pignon, Jean-Christophe ^{[4
]}

Wang, Binbin ^{[5
]}

Wang, Jinzeng ^{[5
]}

Shukla, Sachet A. ^{[6
]}

Dou, Ruoxu ^{[7
]}

Chen, Qianming ^{[3
]}

Hodi, F. Stephen ^{[8
]}

Choueiri, Toni K. ^{[9
]}

Wu, Catherine ^{[6
]}

Hacohen, Nir ^{[10
]}

Signoretti, Sabina ^{[4
]}

Liu, Jun S. ^{[2
]}

Liu, X. Shirley ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[2] Harvard Univ, Dept Stat, Boston, MA 02115 USA

[3] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610064, Peoples R China

[4] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[5] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China

[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[7] Sun Yat Sen Univ, Dept Colorectal Surg, Affiliated Hosp 6, Guangzhou 510275, Guangdong, Peoples R China

[8] Harvard Univ, Sch Med, Ctr ImmunoOncol, Boston, MA USA

[9] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA

[10] Massachusetts Gen Hosp, Ctr Canc Immunotherapy, Boston, MA 02114 USA

来源：

NATURE GENETICS | 2016年 / 48卷 / 07期

基金：

中国国家自然科学基金;

关键词：

RNA-SEQ READS; ANTIGEN; BLOCKADE; SEQUENCE; RECOGNITION; RECEPTORS; AFFINITY; LENGTH;

D O I：

10.1038/ng.3581

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

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.

引用

页码：725 / +

页数：11

共 45 条

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