000299000 001__ 299000 000299000 005__ 20250318095036.0 000299000 0247_ $$2doi$$a10.1016/j.canlet.2025.217581 000299000 0247_ $$2pmid$$apmid:39983894 000299000 0247_ $$2ISSN$$a0304-3835 000299000 0247_ $$2ISSN$$a1872-7980 000299000 037__ $$aDKFZ-2025-00410 000299000 041__ $$aEnglish 000299000 082__ $$a570 000299000 1001_ $$aAbooali, Maryam$$b0 000299000 245__ $$aIntracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment. 000299000 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2025 000299000 3367_ $$2DRIVER$$aarticle 000299000 3367_ $$2DataCite$$aOutput Types/Journal article 000299000 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1742287798_3582 000299000 3367_ $$2BibTeX$$aARTICLE 000299000 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000299000 3367_ $$00$$2EndNote$$aJournal Article 000299000 500__ $$a2025 Apr 28;616:217581 000299000 520__ $$aV-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. 000299000 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0 000299000 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000299000 7001_ $$0P:(DE-He78)0b6e32bf4b6d335c6b11d5edaef8bfd3$$aSchlichtner, Stephanie$$b1$$udkfz 000299000 7001_ $$aLei, Xi$$b2 000299000 7001_ $$aAliu, Nijas$$b3 000299000 7001_ $$aRuggiero, Sabrina$$b4 000299000 7001_ $$0P:(DE-HGF)0$$aLoges, Sonia$$b5 000299000 7001_ $$0P:(DE-He78)62a3cc13c7db450aa0e711ce99b43d7b$$aZiegler, Martin$$b6$$udkfz 000299000 7001_ $$0P:(DE-He78)470d596989d1c5c31fdaa5a2b638e5ae$$aHertel, Franziska$$b7$$udkfz 000299000 7001_ $$aVolckmar, Anna-Lena$$b8 000299000 7001_ $$aStenzinger, Albrecht$$b9 000299000 7001_ $$aChristopoulos, Petros$$b10 000299000 7001_ $$aThomas, Michael$$b11 000299000 7001_ $$aKlenova, Elena$$b12 000299000 7001_ $$aMeyer, N Helge$$b13 000299000 7001_ $$aBoussios, Stergios$$b14 000299000 7001_ $$aHeaton, Nigel$$b15 000299000 7001_ $$aZen, Yoh$$b16 000299000 7001_ $$aZamalloa, Ane$$b17 000299000 7001_ $$aChokshi, Shilpa$$b18 000299000 7001_ $$aUrbani, Luca$$b19 000299000 7001_ $$aRichard, Sophie$$b20 000299000 7001_ $$aKirubendran, Kavitha$$b21 000299000 7001_ $$aHussain, Rohanah$$b22 000299000 7001_ $$aSiligardi, Giuliano$$b23 000299000 7001_ $$aCholewa, Dietmar$$b24 000299000 7001_ $$aBerger, Steffen M$$b25 000299000 7001_ $$aYasinska, Inna M$$b26 000299000 7001_ $$aFasler-Kan, Elizaveta$$b27 000299000 7001_ $$aSumbayev, Vadim V$$b28 000299000 773__ $$0PERI:(DE-600)2004212-7$$a10.1016/j.canlet.2025.217581$$gp. 217581 -$$p217581$$tCancer letters$$v616$$x0304-3835$$y2025 000299000 909CO $$ooai:inrepo02.dkfz.de:299000$$pVDB 000299000 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0b6e32bf4b6d335c6b11d5edaef8bfd3$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000299000 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ 000299000 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)62a3cc13c7db450aa0e711ce99b43d7b$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ 000299000 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)470d596989d1c5c31fdaa5a2b638e5ae$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ 000299000 9131_ $$0G:(DE-HGF)POF4-311$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vZellbiologie und Tumorbiologie$$x0 000299000 9141_ $$y2025 000299000 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2024-12-16$$wger 000299000 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCANCER LETT : 2022$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-16 000299000 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCANCER LETT : 2022$$d2024-12-16 000299000 9201_ $$0I:(DE-He78)A420-20160331$$kA420$$lPersonalisierte Medizinische Onkologie$$x0 000299000 980__ $$ajournal 000299000 980__ $$aVDB 000299000 980__ $$aI:(DE-He78)A420-20160331 000299000 980__ $$aUNRESTRICTED