Landscape of tumor-infiltrating T cell repertoire of human cancers

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 Wu, Nir Hacohen, Sabina Signoretti, Jun S. Liu, X. Shirley Liu

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)725-732
Number of pages8
JournalNature Genetics
Volume48
Issue number7
DOIs
StatePublished - Jul 1 2016

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Complementarity Determining Regions
T-Lymphocytes
Neoplasms
Mutation
Kidney Neoplasms
Testicular Neoplasms
Tumor Burden
Brain Neoplasms
Blood Cells
RNA
Antigens
Amino Acids
Peptides
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Li, B., Li, T., Pignon, J. C., Wang, B., Wang, J., Shukla, S. A., ... Liu, X. S. (2016). Landscape of tumor-infiltrating T cell repertoire of human cancers. Nature Genetics, 48(7), 725-732. https://doi.org/10.1038/ng.3581

Landscape of tumor-infiltrating T cell repertoire of human cancers. / Li, Bo; Li, Taiwen; Pignon, Jean Christophe; Wang, Binbin; Wang, Jinzeng; Shukla, Sachet A.; Dou, Ruoxu; Chen, Qianming; Hodi, F. Stephen; Choueiri, Toni K.; Wu, Catherine; Hacohen, Nir; Signoretti, Sabina; Liu, Jun S.; Liu, X. Shirley.

In: Nature Genetics, Vol. 48, No. 7, 01.07.2016, p. 725-732.

Research output: Contribution to journalArticle

Li, B, Li, T, Pignon, JC, Wang, B, Wang, J, Shukla, SA, Dou, R, Chen, Q, Hodi, FS, Choueiri, TK, Wu, C, Hacohen, N, Signoretti, S, Liu, JS & Liu, XS 2016, 'Landscape of tumor-infiltrating T cell repertoire of human cancers', Nature Genetics, vol. 48, no. 7, pp. 725-732. https://doi.org/10.1038/ng.3581
Li B, Li T, Pignon JC, Wang B, Wang J, Shukla SA et al. Landscape of tumor-infiltrating T cell repertoire of human cancers. Nature Genetics. 2016 Jul 1;48(7):725-732. https://doi.org/10.1038/ng.3581
Li, Bo ; Li, Taiwen ; Pignon, Jean Christophe ; Wang, Binbin ; Wang, Jinzeng ; Shukla, Sachet A. ; Dou, Ruoxu ; Chen, Qianming ; Hodi, F. Stephen ; Choueiri, Toni K. ; Wu, Catherine ; Hacohen, Nir ; Signoretti, Sabina ; Liu, Jun S. ; Liu, X. Shirley. / Landscape of tumor-infiltrating T cell repertoire of human cancers. In: Nature Genetics. 2016 ; Vol. 48, No. 7. pp. 725-732.
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