Format

Send to

Choose Destination
Nat Genet. 2016 Jul;48(7):725-32. doi: 10.1038/ng.3581. Epub 2016 May 30.

Landscape of tumor-infiltrating T cell repertoire of human cancers.

Author information

1
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
2
Department of Statistics, Harvard University, Boston, Massachusetts, USA.
3
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
4
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
5
School of Life Science and Technology, Tongji University, China, Shanghai, China.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
7
Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
8
Center for ImmunoOncology, Harvard Medical School, Boston, Massachusetts, USA.
9
Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
10
Center for Cancer Immunotherapy, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

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.

PMID:
27240091
PMCID:
PMC5298896
DOI:
10.1038/ng.3581
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center