title: Landscape of tumor-infiltrating T cell repertoire of human cancers.
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.
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Statistics, Harvard University, Boston, Massachusetts, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Taiwen
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Pignon
authors.affiliation: School of Life Science and Technology, Tongji University, China, Shanghai, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Tongji University, China, Shanghai, China.
authors.forename: Jinzeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Sachet A
authors.initials: SA
authors.lastname: Shukla
authors.affiliation: Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ruoxu
authors.initials: R
authors.lastname: Dou
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Center for ImmunoOncology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Wu
authors.affiliation: Center for Cancer Immunotherapy, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Department of Statistics, Harvard University, Boston, Massachusetts, USA.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Statistics, Harvard University, Boston, Massachusetts, USA.
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D022801:Complementarity Determining Regions / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D022801:Complementarity Determining Regions; D006680:HLA Antigens; D009363:Neoplasm Proteins; C404944:PRAME protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta