Single cell RNA-seq and TCR-seq of T cell responses against DNAJB1-PRKACA

The DNAJB1-PRKACA fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma (FL-HCC), a lethal disease lacking specific therapies. Here, we report on the identification, characterization and first immunotherapeutic application of HLA-presented neoantigens specific for the DNAJB1-PRKACA fusion transcript in FL-HCC. To characterize the T cell response against DNAJB1-PRKACA-derived HLA class I and HLA class II ligands, single cell RNA sequencing (scRNA-seq) and single cell TCR profiling from CD4+ and CD8+ T cells were performed using 10x Genomics single cell immune profiling. In this study, we analyzed the expressional profile and T cell receptor (TCR) repertoire of CD4+ T cells from a patient with FL-HCC after vaccination with a personalized DNAJB1-PRKACA-derived peptide vaccine. Furthermore we analyzed flow cytometry-sorted PA*24-specific CD8+ T cells from two healthy volunteers (P3 and P4) after in vitro aAPC priming. Single cell RNA sequencing (scRNA-seq) and single cell TCR profiling were performed using 10x Genomics single cell immune profiling.