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Immunosuppressive Traits of the Hybrid Epithelial/Mesenchymal Phenotype

Sahoo, S and Nayak, SP and Hari, K and Purkait, P and Mandal, S and Kishore, A and Levine, H and Jolly, MK (2021) Immunosuppressive Traits of the Hybrid Epithelial/Mesenchymal Phenotype. In: Frontiers in Immunology, 12 .

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Official URL: https://doi.org/10.3389/fimmu.2021.797261


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 simulations for the network consisting of SLUG, ZEB1, miR-200, CDH1 and PD-L1, 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. Copyright © 2021 Sahoo, Nayak, Hari, Purkait, Mandal, Kishore, Levine and Jolly.

Item Type: Journal Article
Publication: Frontiers in Immunology
Publisher: Frontiers Media S.A.
Additional Information: The copyright for this article belongs to the Author.
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
UG Programme
Date Deposited: 12 Jan 2022 05:46
Last Modified: 12 Jan 2022 05:46
URI: http://eprints.iisc.ac.in/id/eprint/70928

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