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Intracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment

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 an...

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Hauptverfasser: Abooali, Maryam (VerfasserIn) , Schlichtner, Stephanie (VerfasserIn) , Lei, Xi (VerfasserIn) , Aliu, Nijas (VerfasserIn) , Ruggiero, Sabrina (VerfasserIn) , Loges, Sonja (VerfasserIn) , Ziegler, Martin (VerfasserIn) , Hertel, Franziska (VerfasserIn) , Volckmar, Anna-Lena (VerfasserIn) , Stenzinger, Albrecht (VerfasserIn) , Christopoulos, Petros (VerfasserIn) , Thomas, Michael (VerfasserIn) , Klenova, Elena (VerfasserIn) , Meyer, N. Helge (VerfasserIn) , Boussios, Stergios (VerfasserIn) , Heaton, Nigel (VerfasserIn) , Zen, Yoh (VerfasserIn) , Zamalloa, Ane (VerfasserIn) , Chokshi, Shilpa (VerfasserIn) , Urbani, Luca (VerfasserIn) , Richard, Sophie (VerfasserIn) , Kirubendran, Kavitha (VerfasserIn) , Hussain, Rohanah (VerfasserIn) , Siligardi, Giuliano (VerfasserIn) , Cholewa, Dietmar (VerfasserIn) , Berger, Steffen M. (VerfasserIn) , Yasinska, Inna M. (VerfasserIn) , Fasler-Kan, Elizaveta (VerfasserIn) , Sumbayev, Vadim V. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 April 2025
In: Cancer letters
Year: 2025, Jahrgang: 616, Pages: 1-13
ISSN:1872-7980
DOI:10.1016/j.canlet.2025.217581
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.canlet.2025.217581
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0304383525001454
Volltext
Verfasserangaben:Maryam Abooali, Stephanie Schlichtner, Xi Lei, Nijas Aliu, Sabrina Ruggiero, Sonia Loges, Martin Ziegler, Franziska Hertel, Anna-Lena Volckmar, Albrecht Stenzinger, Petros Christopoulos, Michael Thomas, Elena Klenova, N. Helge Meyer, Stergios Boussios, Nigel Heaton, Yoh Zen, Ane Zamalloa, Shilpa Chokshi, Luca Urbani, Sophie Richard, Kavitha Kirubendran, Rohanah Hussain, Giuliano Siligardi, Dietmar Cholewa, Steffen M. Berger, Inna M. Yasinska, Elizaveta Fasler-Kan, Vadim V. Sumbayev
Beschreibung
Zusammenfassung: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.
Beschreibung:Sonja Loges ist fälschlich als "Sonia Loges" geschrieben
Online verfügbar: 20. Februar 2025, Artikelversion: 27. Februar 2025
Gesehen am 27.05.2025
Beschreibung:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2025.217581

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