Bidirectional crosstalk between epithelial–mesenchymal plasticity and IFN γ -induced PD-L1 expression promotes tumour progression

Epithelial–mesenchymal transition (EMT) and immunoevasion through upregulation of programmed death-ligand 1 (PD-L1) are important drivers of cancer progression. While EMT has been proposed to facilitate PD-L1-mediated immunosuppression, molecular mechanisms of their interaction remain obscure. Here,...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Royal Society open science Ročník 9; číslo 11; s. 220186
Hlavní autoři: Burger, Gerhard A., Nesenberend, Daphne N., Lems, Carlijn M., Hille, Sander C., Beltman, Joost B.
Médium: Journal Article
Jazyk:angličtina
Vydáno: The Royal Society 02.11.2022
Témata:
Biochemistry, Cellular and Molecular Biology
epithelial-mesenchymal transition (EMT)
immune evasion
interferon gamma
PD-L1
ISSN:2054-5703, 2054-5703
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Epithelial–mesenchymal transition (EMT) and immunoevasion through upregulation of programmed death-ligand 1 (PD-L1) are important drivers of cancer progression. While EMT has been proposed to facilitate PD-L1-mediated immunosuppression, molecular mechanisms of their interaction remain obscure. Here, we provide insight into these mechanisms by proposing a mathematical model that describes the crosstalk between EMT and interferon gamma (IFN γ )-induced PD-L1 expression. Our model shows that via interaction with microRNA-200 (miR-200), the multi-stability of the EMT regulatory circuit is mirrored in PD-L1 levels, which are further amplified by IFN γ stimulation. This IFN γ -mediated effect is most prominent for cells in a fully mesenchymal state and less strong for those in an epithelial or partially mesenchymal state. In addition, bidirectional crosstalk between miR-200 and PD-L1 implies that IFN γ stimulation allows cells to undergo EMT for lower amounts of inducing signal, and the presence of IFN γ accelerates EMT and decelerates mesenchymal–epithelial transition (MET). Overall, our model agrees with published findings and provides insight into possible mechanisms behind EMT-mediated immune evasion, and primary, adaptive, or acquired resistance to immunotherapy. Our model can be used as a starting point to explore additional crosstalk mechanisms, as an improved understanding of these mechanisms is indispensable for developing better diagnostic and therapeutic options for cancer patients.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.6251541.
These authors have contributed equally to this work.
ISSN:2054-5703
2054-5703
DOI:10.1098/rsos.220186