B cell-reactive neoantigens boost antitumor immunity.

Area of Science:

• Immunology
• Oncology
• Bioinformatics

Background:

• B cell involvement in neoantigen-driven antitumor immunity is poorly understood due to prediction challenges.
• Identifying B cell epitopes is critical for understanding and enhancing anti-cancer immune responses.

Purpose of the Study:

• To develop and validate a method for predicting B cell neoepitopes.
• To investigate the role of B cell neoepitopes in antitumor immunity and their clinical relevance.

Main Methods:

• Characterized >437,000 peptides for IgG binding and >370 million B cell receptor (BCR) clones.
• Utilized single-cell BCR sequencing for method validation.
• Performed genomic analysis of The Cancer Genome Atlas (TCGA) samples and meta-analysis of personalized vaccine trials.

Main Results:

• Developed a method to identify B cell epitopes, validated with SARS-CoV-2 vaccination data.
• Demonstrated that B cell neoepitopes enhance immune responses, promote BCR expansion, and drive tumor regression in mouse models.
• Found an inverse correlation between predicted B cell reactivity and mutation allele frequencies in TCGA samples, suggesting B cell-mediated neoantigen elimination.
• Highlighted the clinical relevance of B cell neoepitope prediction in checkpoint blockade therapy and potential improvement in personalized vaccine efficacy.

Conclusions:

• B cell-reactive neoantigens play a significant role in antitumor immunity.
• The developed method for B cell neoepitope prediction has implications for cancer immunotherapy and vaccine development.