Immunogenic cryptic peptides dominate the antigenic landscape of ovarian cancer
Details
Publication Year 2025-02,Volume 11,Issue #8,Page eads7405
Journal Title
Science Advances
Publication Type
Research article
Abstract
Increased infiltration of CD3(+) and CD8(+) T cells into ovarian cancer (OC) is linked to better prognosis, but the specific antigens involved are unclear. Recent reports suggest that HLA class I can present peptides from noncoding genomic regions, known as noncanonical or cryptic peptides, but their immunogenicity is underexplored. To address this, we used immunopeptidomic analysis and RNA sequencing on five metastatic OC samples, which identified 311 cryptic peptides (40 to 83 per patient). Despite comprising less than 1% of total peptides, cryptic peptides from noncoding transcripts emerged as the predominant antigen class when compared to the other major classes of known tumor-specific and tumor-associated antigens in OC samples. Notably, nearly 70% of the prioritized cryptic peptides elicited T cell activation, as evidenced by increased 4-1BB and IFN-γ expression in autologous CD8(+) T cells. This study reveals noncoding cryptic peptides as an important class of immunogenic antigens in OC.
Keywords
Humans; *Ovarian Neoplasms/immunology/genetics; Female; *Antigens, Neoplasm/immunology; *Peptides/immunology/chemistry; *CD8-Positive T-Lymphocytes/immunology; Interferon-gamma/metabolism; Lymphocyte Activation/immunology
Department(s)
Laboratory Research
Open Access at Publisher's Site
https://doi.org/10.1126/sciadv.ads7405
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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