Breast Cancer Neoantigens Can Induce CD8⁺ T-Cell Responses and Antitumor Immunity

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Next-generation sequencing (NGS) advances cancer research by revealing tumor biology and mutational profiles.
• Cancer neoantigens are crucial targets for cancer immunotherapy.

Purpose of the Study:

• To evaluate the relevance and immunogenicity of cancer neoantigens in human breast cancers.
• To assess the potential of neoantigen-targeted therapies for breast cancer.

Main Methods:

• Whole-exome sequencing of patient-derived breast cancer xenografts (WHIM30, WHIM35, WHIM37) and matched normal cells.
• Computational identification and prioritization of HLA class I-restricted neoantigens.
• Validation using peptide-binding assays, CD8+ T-cell recognition assays, and preclinical antitumor immunity models.

Main Results:

• Identified thousands of nonsynonymous somatic mutations across three breast cancer xenografts.
• Demonstrated that breast cancer neoantigens are recognized by the human immune system.
• Showed that CD8+ T cells targeting prioritized neoantigens conferred protection against autologous tumor xenografts in mice.

Conclusions:

• NGS and epitope prediction can effectively identify and prioritize neoantigens for immune targeting in breast cancer.
• Breast cancer neoantigens hold promise as targets for developing novel immunotherapies.