Comprehensive characterizations of immune receptor repertoire in tumors and cancer immunotherapy studies

Abstract We applied our computational algorithm TRUST4 to assemble immune receptor (TCR/BCR) repertoires from approximately twelve thousand RNA-seq samples from The Cancer Genome Atlas (TCGA) and seven immunotherapy studies. From over 35 million assembled complete complementary-determining region 3 (CDR3) sequences, we observed that the expression of CCL5 and MZB1 are 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.