Epithelial-Mesenchymal Transition Inversely Associates With Immune Activity in Breast Cancer Tumour Immune Microenvironment

The epithelial to mesenchymal transition (EMT) is a major mechanism of resistance to cancer therapy, including immunotherapy in breast cancer. Recent studies highlighted the role of the EMT program in regulating immune checkpoints; however, the overall immune activity during EMT of carcinoma remains to be shown. Using in-silico data analysis on a large cohort of breast cancer samples from The Cancer Genome Atlas (TCGA) and measuring immune activities across various EMT scores, we found that an increasing EMT score reduces immune cells infiltration and activity, turning an immune infiltrated ‘hot’ tumor microenvironment (TME) to a ‘cold’ and less immune infiltrated TME. Remarkably, the high EMT score and expression of EMT related genes negatively associated with infiltration and activity of various immune cells particularly CD8+ T cells, while increased intratumoral heterogeneity level, infiltration of Treg cells, and M2 macrophages in TME. These data revealed the crucial role of the EMT program in regulating immune-suppression in the tumor-immune microenvironment (TIME) by reducing immune activity and highlighting the potential application of EMT score as a biomarker for the responsiveness of breast cancer patients to immunotherapy.