Multiomics prediction and immunogenic validation of personalized neoantigens in cholangiocarcinoma patients.

BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive biliary tract cancer with limited treatment options, underscoring the need for breakthrough precision therapies. Neoantigen-based therapy is a promising novel strategy for cancer treatment. This study investigates the potential of neoantigen peptides in CCA, emphasizing their role in personalized immunotherapy and providing insights for vaccine design. METHODS: Paired samples from 33 CCA patients underwent whole-exome sequencing and RNA sequencing to profile the mutational and neoantigen landscape. Besides, personalized neoantigen peptides were synthesized and immunogenicity was validated through enzyme-linked immunospot assay. Meanwhile, corresponding T cell receptor (TCR) sequences were predicted by bioinformatics. RESULTS: TP53 was the most frequently mutated gene (57.58%) and a significant positive correlation between tumor mutational burden and neoantigen load was observed (r = 0.6511, p CONCLUSIONS: Our findings show that candidate immunogenic neoantigen peptides can be identified in CCA and are supported by proof-of-concept functional validation. Together, these results provide a framework for the downstream validation of neoantigen targets and the development of personalized immunotherapy approaches.