Landscape of tumor-infiltrating T cell repertoire of human cancers

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Complementarity Determining Regions / genetics*
  • HLA Antigens / genetics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Mutation / genetics*
  • Neoplasm Proteins / genetics*
  • Neoplasms / genetics*
  • Neoplasms / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*


  • Antigens, Neoplasm
  • Complementarity Determining Regions
  • HLA Antigens
  • Neoplasm Proteins
  • PRAME protein, human
  • Receptors, Antigen, T-Cell, alpha-beta