DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity in vivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.

A tactile approach to introduce the skin autoimmune disease psoriasis to the general public and the vision-impaired community.

Scientific outreach activities play an important role in disseminating knowledge, connecting the general public to research and breaking down scientific skepticism barriers. However, the vision-impaired community is often disadvantaged when the most common audio-visual approach of scientific communication is applied. Here we integrated tactile clues in the scientific communication of immune processes involved in the autoimmune skin disease psoriasis. We fostered the involvement of the vision-impaired community through interactive experiences, including tactile scientific origami art, a haptic poster and wood-carved molecular models. Readily accessible science communication that engages a number of senses is a critical step toward making science more inclusive and engaging for individuals with a wide range of sensory abilities. The approach of the 2023 Monash Sensory Science exhibition aligns with the principles of equity, diversity and inclusion and helps to empower a more informed and scientifically literate public.