Presentation of DNAJB1-PRKACA fusion neoantigens by different HLA class I alleles

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in this disease is its highly conserved driver mutation: a gene fusion between DNAJB1 and PRKACA, which is expressed in virtually all FLC tumors and could be an ideal neoantigen target for immunotherapy. In this study, we aimed to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) as candidates for novel cellular immunotherapies. Although fusion-specific T cells in FLC appear to be rare, we nevertheless defined an endogenous functional T cell response in an FLC patient.