Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides

Emerging evidence shows that previously defined noncoding regions of the genome may encode cryptic antigen peptides that can bind to HLA and stimulate adaptive immunity against tumors. However, the significance and mechanisms of these cryptic antigens are still unclear. This study analyzed the HLA class I peptidome and ribosome sequencing data from human breast cancer samples. They identified HLA-binding cryptic antigen peptides that were translated in a noncanonical way by the circular RNA circFAM53B specifically in tumor cells. These cryptic peptides efficiently primed naive CD4+ and CD8+ T cells in an antigen-specific manner and induced anti-tumor immunity. Higher expression of circFAM53B and its encoded peptides was associated with increased tumor-specific CD8+ T cell infiltration and better survival in breast cancer and melanoma patients. Mechanistically, the circFAM53B-encoded peptides had strong binding affinity to both HLA class I and II molecules. Vaccines containing the tumor-specific circRNA or its encoded peptides induced enhanced tumor-specific cytotoxic T cells and effective tumor control in mouse models of breast cancer and melanoma. <a href="https://medium.com/@axialxyz/tumour-circular-rnas-elicit-anti-tumour-immunity-by-encoding-cryptic-peptides-cd6f1ace023e">Read More</a>