Impact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival

• Main Authors: Wenjing Li, Amei Amei, Francis Bui, Saba Norouzifar, Lingeng Lu, Zuoheng Wang
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Cancers
• Subjects: breast cancer; neoantigen expression; T-cell activation status; DNA repair gene; overall survival
• Online Access: https://www.mdpi.com/2072-6694/13/12/2879

Neoantigens are derived from tumor-specific somatic mutations. Neoantigen-based synthesized peptides have been under clinical investigation to boost cancer immunotherapy efficacy. The promising results prompt us to further elucidate the effect of neoantigen expression on patient survival in breast cancer. We applied Kaplan–Meier survival and multivariable Cox regression models to evaluate the effect of neoantigen expression and its interaction with T-cell activation on overall survival in a cohort of 729 breast cancer patients. Pearson’s chi-squared tests were used to assess the relationships between neoantigen expression and clinical pathological variables. Spearman correlation analysis was conducted to identify correlations between neoantigen expression, mutation load, and DNA repair gene expression. <i>ERCC</i>1, <i>XPA</i>, and <i>XPC</i> were negatively associated with neoantigen expression, while <i>BLM</i>, <i>BRCA</i>2, <i>MSH</i>2, <i>XRCC</i>2, <i>RAD</i>51<i>, CHEK</i>1, and <i>CHEK</i>2 were positively associated with neoantigen expression. Based on the multivariable Cox proportional hazard model, patients with a high level of neoantigen expression and activated T-cell status showed improved overall survival. Similarly, in the T-cell exhaustion and progesterone receptor (PR) positive subgroups, patients with a high level of neoantigen expression showed prolonged survival. In contrast, there was no significant difference in the T-cell activation and PR negative subgroups. In conclusion, neoantigens may serve as immunogenic agents for immunotherapy in breast cancer.