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

SIMPLE SUMMARY: Neoantigens are novel proteins presented on the cell surface and derived from the accumulation of somatic mutations in tumor cells. They can be recognized by the immune system and may play a crucial role in boosting immune responses against tumor cells. The impact of neoantigen expression and T-cell activation status on overall survival was investigated in a breast cancer cohort. We found that high neoantigen expression and T-cell activation status was correlated with improved patient survival in the study population. This result supports that neoantigens are promising to serve as immunogenic agents for immunotherapy in breast cancer. ABSTRACT: 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. ERCC1, XPA, and XPC were negatively associated with neoantigen expression, while BLM, BRCA2, MSH2, XRCC2, RAD51, CHEK1, and CHEK2 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.