Journal
VIRAL IMMUNOLOGY
Volume 36, Issue 10, Pages 669-677Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/vim.2023.0078
Keywords
CDR3-HCV antigen chemical complementarity; liver cancer; T cell receptor-beta; immunoglobulins
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In this study, a chemical complementarity scoring algorithm was used to investigate the relationship between adaptive immune receptors in hepatocellular carcinoma microenvironments and disease outcomes. The results indicated that CDR3 sequences can serve as biomarkers for patient stratification in HCC and as guides for therapeutic development.
To better understand how adaptive immune receptors (IRs) in hepatocellular carcinoma (HCC) microenvironments are related to disease outcomes, we employed a chemical complementarity scoring algorithm to quantify electrostatic complementarity between HCC tumor TRB or IGH complementarity-determining region 3 (CDR3) amino acid (AA) sequences and previously characterized hepatitis C virus (HCV) epitopes. High electrostatic complementarity between HCC-resident CDR3s and 12 HCV epitopes was associated with greater survival probabilities, as indicated by two distinct HCC IR CDR3 datasets. Two of the HCV epitopes, HCV*71871 (TRB) and HCV*13458 (IGH), were also determined to represent significantly larger electrostatic CDR3-HCV epitope complementarity in HCV-positive HCC cases, compared with HCV-negative HCC cases, with the CDR3s representing yet a third, independent HCC dataset. Overall, the results indicated the utility of CDR3 AA sequences as biomarkers for HCC patient stratification and as potential guides for the development of therapeutic reagents.
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