Abooali, Maryam, Schlichtner, Stephanie, Lei, Xi, Aliu, Nijas, Ruggiero, Sabrina, Loges, Sonia, Ziegler, Martin, Hertel, Franziska, Volckmar, Anna-Lena, Stenzinger, Albrecht, and others. (2025) Intracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment. Cancer Letters, 616 . Article Number 217581. ISSN 0304-3835. (doi:10.1016/j.canlet.2025.217581) (KAR id:108856)
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| Official URL: https://doi.org/10.1016/j.canlet.2025.217581 |
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Abstract
V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms of regulation of VISTA activity and functions by factors of tumour microenvironment (TME) remain unclear and understanding these processes is required in order to develop successful personalised cancer immunotherapeutic strategies and approaches. Here we report for the very first time that VISTA interacts with another immune checkpoint protein galectin-9 inside the cell most likely facilitating its interaction with TGF-β-activated kinase 1 (TAK1). This process is required for protection of lysosomes, which is crucial for many cell types and tissues. We found that VISTA expression can be differentially controlled by crucial factors present in TME, such as transforming growth factor beta type 1 (TGF-β) and hypoxia as well as other factors activating hypoxic signalling. We confirmed that involvement of these important pathways modulated by TME differentially influences VISTA expression in different cell types. These networks include: TGF-β-Smad3 pathway, TAK1 (TGF-β-activated kinase 1) or apoptosis signal-regulating kinase 1 (ASK1)-induced activation of activating transcription factor 2 (ATF-2) and hypoxic signalling pathway. Based on this work we determined the five critical functions of VISTA and the role of TME factors in controlling (modulating or downregulating) VISTA expression.
| Item Type: | Article |
|---|---|
| DOI/Identification number: | 10.1016/j.canlet.2025.217581 |
| Subjects: |
R Medicine R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Divisions > Division of Natural Sciences > Medway School of Pharmacy |
| Funders: |
University of Kent (https://ror.org/00xkeyj56)
Diamond Light Source (https://ror.org/05etxs293) |
| SWORD Depositor: | JISC Publications Router |
| Depositing User: | JISC Publications Router |
| Date Deposited: | 25 Feb 2025 14:34 UTC |
| Last Modified: | 07 Mar 2025 15:01 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/108856 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Abooali, Maryam.
| Creator's ORCID: | |
|---|---|
| CReDIT Contributor Roles: | Investigation, Methodology, Validation, Conceptualisation |
Lei, Xi.
| Creator's ORCID: | |
|---|---|
| CReDIT Contributor Roles: | Investigation |
Yasinska, Inna M..
| Creator's ORCID: | |
|---|---|
| CReDIT Contributor Roles: | Investigation, Methodology, Writing - review and editing, Conceptualisation |
Sumbayev, Vadim V..
| Creator's ORCID: |
 https://orcid.org/0000-0002-9404-5626
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|---|---|
| CReDIT Contributor Roles: | Data curation, Investigation, Methodology, Supervision, Resources, Writing - original draft, Conceptualisation, Funding acquisition, Project administration |
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