TY - JOUR T1 - Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype JF - bioRxiv DO - 10.1101/2021.06.21.449285 SP - 2021.06.21.449285 AU - Sarthak Sahoo AU - Sonali Priyadarshini Nayak AU - Kishore Hari AU - Prithu Purkait AU - Susmita Mandal AU - Akash Kishore AU - Herbert Levine AU - Mohit Kumar Jolly Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/08/20/2021.06.21.449285.abstract N2 - Recent preclinical and clinical data suggests enhanced metastatic fitness of hybrid epithelial/ mesenchymal (E/M) phenotypes, but mechanistic details regarding their survival strategies during metastasis remain unclear. Here, we investigate immune-evasive strategies of hybrid E/M states. We construct and simulate the dynamics of a minimalistic regulatory network encompassing the known associations among regulators of EMT (epithelial-mesenchymal transition) and PD-L1, an established immune-suppressor. Our model simulations, integrated with single-cell and bulk RNA-seq data analysis, elucidate that hybrid E/M cells can have high levels of PD-L1, similar to those seen in cells with a full EMT phenotype, thus obviating the need for cancer cells to undergo a full EMT to be immune-evasive. Specifically, in breast cancer, we show the co-existence of hybrid E/M phenotypes, enhanced resistance to anti-estrogen therapy and increased PD-L1 levels. Our results underscore how the emergent dynamics of interconnected regulatory networks can coordinate different axes of cellular fitness during metastasis.Competing Interest StatementThe authors have declared no competing interest. ER -