Comprehensive Characterizations of Immune Receptor Repertoire in Tumors and Cancer Immunotherapy Studies

Cancer Immunol Res. 2022 Jul 1;10(7):788-799. doi: 10.1158/2326-6066.CIR-21-0965.


We applied our computational algorithm TRUST4 to assemble immune receptor (T-cell receptor/B-cell receptor) repertoires from approximately 12,000 RNA sequencing samples from The Cancer Genome Atlas and seven immunotherapy studies. From over 35 million assembled complete complementary-determining region 3 sequences, we observed that the expression of CCL5 and MZB1 is the most positively correlated genes with T-cell clonal expansion and B-cell clonal expansion, respectively. We analyzed amino acid evolution during B-cell receptor somatic hypermutation and identified tyrosine as the preferred residue. We found that IgG1+IgG3 antibodies together with FcRn were associated with complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity or phagocytosis. In addition to B-cell infiltration, we discovered that B-cell clonal expansion and IgG1+IgG3 antibodies are also correlated with better patient outcomes. Finally, we created a website, VisualizIRR, for users to interactively explore and visualize the immune repertoires in this study. See related Spotlight by Liu and Han, p. 786.

Publication types

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

MeSH terms

  • Humans
  • Immunoglobulin G / immunology
  • Immunologic Factors
  • Immunotherapy
  • Neoplasms* / therapy
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Immunologic / genetics


  • Immunoglobulin G
  • Immunologic Factors
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic