B cell–reactive neoantigens boost antitumor immunity
B cell involvement in neoantigen-driven antitumor immunity remains largely unexplored because of challenges in predicting B cell responses. Here, we developed a method to identify B cell epitopes by characterizing >437,000 peptides tested for IgG binding and >370 million B cell receptor (BCR) clones. Our single-cell BCR sequencing of pre- and post-severe acute respiratory syndrome coronavirus 2 vaccination validates the performance of this method. Mouse vaccination experiments demonstrate that B cell neoepitopes enhance immune responses, driving BCR expansion and tumor regression. Genomic analysis of >8000 The Cancer Genome Atlas (TCGA) samples reveals an inverse correlation between predicted B cell reactivity and mutation allele frequencies, indicating B cell-mediated neoantigen elimination. Applying our multiomics model to checkpoint blockade responses in 2074 patients highlights the clinical relevance of B cell neoepitope prediction. A meta-analysis of 11 personalized vaccine trials involving 1739 neoantigens suggests that incorporating B cell neoepitopes may improve vaccination efficacy. These results underscore the significance of B cell-reactive neoantigens in antitumor immunity.
Authors
- Jung Kyoon Choi (ORCID: https://orcid.org/0000-0003-2077-8947)
- Suhwan Chang (ORCID: https://orcid.org/0000-0002-0282-0120)
- Se‐Hoon Lee (ORCID: https://orcid.org/0000-0002-9219-3350)
- Hye-Yeong Jo (ORCID: https://orcid.org/0000-0002-2343-7729)
- Hyun‐Young Park (ORCID: https://orcid.org/0000-0002-6698-7368)
- Jinhyeon An (ORCID: https://orcid.org/0000-0001-7905-3321)
- Hongui Cha (ORCID: https://orcid.org/0000-0003-2404-1838)
- Eun Ji Lee (ORCID: https://orcid.org/0000-0001-8264-080X)
- Min Ju Kim (ORCID: https://orcid.org/0000-0001-5901-3242)
- Dae-Yeon Cho (ORCID: https://orcid.org/0000-0003-1313-8124)
- Sang Cheol Kim (ORCID: https://orcid.org/0000-0003-4389-9178)
- Inkyung Shin (ORCID: https://orcid.org/0009-0007-2715-4447)
- So-Yeon Kim (ORCID: https://orcid.org/0009-0000-0737-4951)
- Jeong Yeon Kim (ORCID: https://orcid.org/0000-0002-8678-4568)
Institutions
- Ulsan College (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Asan Medical Center (KR)
- Samsung Medical Center (KR)
- University of Ulsan (KR)
- Korea National Institute of Health (KR)
- Korea Disease Control and Prevention Agency (KR)
- CrystalGenomics (South Korea) (KR)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Science Advances
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1126/sciadv.adx8303
- Primary Topic
- vaccines and immunoinformatics approaches
- Type
- article
- Field-Weighted Citation Impact
- 0.00