Abstract 3857: Tumor-extrinsic BIRC3 promote sensitivity to checkpoint inhibition immunotherapy in breast cancer

Abstract

Abstract Baculoviral IAP repeat containing 3 (BIRC3) protein play a critical role in breast cancer. Blocking BIRC3 cause apoptosis in tumor cells, but its correlation with tumor immunity remains elusive. TCGA databases were employed to examine the expression of BIRC3 in breast cancer. The correlation between BIRC3 expression and T cell infiltration and function was employed in breast cancer tissues (n=92) by immunohistochemistry. Birinapant, a selective BIRC3 inhibitor, was then used to investigate the effect of BIRC3 blockade on tumor immune microenvironment (TIME) landscape of breast cancer syngeneic mouse models by flow cytometry. Survival analysis suggested that the low expression of BIRC3 was associated with poor overall survival (OS). Additionally, we uncovered the close association between BIRC3 expression and the profiles of immune cells in breast cancer microenvironment based on the TCGA dataset. Interestingly, we found that BIRC3 expression was positively correlated with cytotoxic T lymphocyte infiltration and T-cell effector function by immunohistochemistry. The in vivo experiments suggested that blocking BIRC3 might convert ‘hot’ tumor into ‘cold’ tumor, which was characterized by a decreased of CD8+ T cell infiltration and inhibition of CD8+T cell function. Furthermore, we observed that BIRC3 blocking combined with immune checkpoint blockade therapy (ICT) greatly restrains immunotherapy efficacy of breast cancer model. Our study revealed a positively association between BIRC3 and anti-tumor immune landscape in breast cancer. Notably, we established a validated prognosis model based on BIRC3 and BIRC3 associated immunomodulators in breast cancer. Citation Format: Dejuan Yang, Jiazheng Sun, Guosheng Ren, Hongzhong Li. Tumor-extrinsic BIRC3 promote sensitivity to checkpoint inhibition immunotherapy in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3857.