Tumour-wide RNA splicing aberrations generate actionable public neoantigens.

ABSTRACT: T cell-based immunotherapies hold promise in treating cancer by leveraging the immune system's recognition of cancer-specific antigens¹. However, their efficacy is limited in tumours with few somatic mutations and substantial intratumoural heterogeneity^2-4. Here we introduce a previously uncharacterized class of tumour-wide public neoantigens originating from RNA splicing aberrations in diverse cancer types. We identified T cell receptor clones capable of recognizing and targeting neoantigens derived from aberrant splicing in GNAS and RPL22. In cases with multi-site biopsies, we detected the tumour-wide expression of the GNAS neojunction in glioma, mesothelioma, prostate cancer and liver cancer. These neoantigens are endogenously generated and presented by tumour cell

SUBMITTER: Kwok DW 

PROVIDER: S-EPMC11903331 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature