Background: The Epithelial-Mesenchymal Transition (EMT) is a defined cellular program associated with the progression and metastasis of breast carcinoma. The immune phenotype and tumour microenvironment are key determinants in the progression of breast carcinoma. This study aims to establish a connection between passage through an EMT and alteration of the expression of markers associated with an immunoevasive phenotype.
Method: Human luminal breast carcinoma cell lines MCF7-Ras and T47D-Ras with doxycycline-inducible EMT transcription factors (EMT-TFs) were analysed by flow cytometry and Western blot for alteration of expression of HLA-ABC and PD-L1 following treatment with doxycycline.
Results: After 6 days of doxycycline treatment, when compared to the Luciferase-expressing control, expression of PD-L1 was increased in MCF7-Ras cells expressing the EMT-TFs Sox9, both Slug and Sox9, and Zeb1. There was no change in expression for cells expressing Twist. After 6 days of doxycycline treatment, T47D-Ras cells expressing both Slug and Sox9 demonstrated a decrease in the expression of HLA-ABC when compared to the Luciferase control. These changes in expression were rescued following withdrawal of doxycycline treatment, with the exception of MCF7-Ras-Slug/Sox9. Changes in expression of HLA-ABC and PD-L1 were accompanied by morphological and biochemical changes associated with the EMT, including a change from ordered epithelial morphology to an elongated, spindle-like morphology, a decrease in the expression of E-Cadherin, and increase in the expression of EMT-TFs.
Conclusion: MCF7 and T47D breast carcinoma cell lines undergoing forced expression of EMT-TFs demonstrate immunoevasive features in association with an EMT. Further research is required to characterise the role of immunoevasion in the EMT program.