{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:38:21Z","timestamp":1790037501701,"version":"4.0.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2RO1 CA177875 and RO1 CA2558451"],"award-info":[{"award-number":["2RO1 CA177875 and RO1 CA2558451"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Angiogenesis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The abnormal tumor vasculature can present a barrier to the infiltration of anti-tumor immune cells, which impairs immune surveillance and response to immunotherapy. Here, we show that genetically deleting the epigenetic factor DNA methyltransferase 1 (\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    ) in endothelial cells (ECs) reduces angiogenesis while imparting profound changes to the tumor immune microenvironment (TIME), including increased proportions of CD4\n                    <jats:sup>+<\/jats:sup>\n                    memory T cells and NK cells. Depleting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, or blocking lymphocyte egress from the lymph nodes, rescues tumor growth in mice with conditional deletion of\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    in ECs (\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    <jats:sup>iECKO<\/jats:sup>\n                    ) and dramatically shortens overall survival, whereas NK cells are dispensable. Tumors implanted in\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    <jats:sup>iECKO<\/jats:sup>\n                    mice show reduced vascular branching, elevated expression of VCAM1, increased vessel-associated T cells, and a shift in vascular specification, including increased proportions of immune-permissive post-capillary venules (PCVs) and interferon-stimulated ECs (IFN-ECs). Deleting\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    in EC cultures strikingly potentiates responses to combinations of IFN\u03b3 and TNF\u03b1 and, notably, up-regulates important T-cell co-stimulatory molecules for memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, including\n                    <jats:italic>Icosl<\/jats:italic>\n                    ,\n                    <jats:italic>Cd40<\/jats:italic>\n                    , and\n                    <jats:italic>Tnfsf4<\/jats:italic>\n                    . Finally, immune checkpoint blockade (ICB) administered to\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    <jats:sup>iECKO<\/jats:sup>\n                    mice with experimental melanoma lung metastasis reduces tumor burden, with some mice showing tumor eradication. Our findings identify endothelial\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    as a key regulator of vascular-mediated anti-tumor immunity, providing a rationale for integrating epigenetic modulation of the vasculature with cancer immunotherapy regimens.\n                  <\/jats:p>","DOI":"10.1007\/s10456-026-10042-y","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:30:09Z","timestamp":1779204609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An epigenetic switch in vascular phenotype augments anti-tumor immunity"],"prefix":"10.1007","volume":"29","author":[{"given":"Dae Joong","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"McGinty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha","family":"Anandh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Riedstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuvraj","family":"Sethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie R.","family":"Rutkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Dudley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"issue":"3","key":"10042_CR1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006536","volume":"2","author":"AC Dudley","year":"2012","unstructured":"Dudley AC (2012) Tumor endothelial cells. Cold Spring Harb Perspect Med 2(3):a006536. https:\/\/doi.org\/10.1101\/cshperspect.a006536","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"3","key":"10042_CR2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s10456-023-09876-7","volume":"26","author":"AC Dudley","year":"2023","unstructured":"Dudley AC, Griffioen AW (2023) Pathological angiogenesis: mechanisms and therapeutic strategies. Angiogenesis 26(3):313\u2013347. https:\/\/doi.org\/10.1007\/s10456-023-09876-7","journal-title":"Angiogenesis"},{"key":"10042_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-025-01187-w","author":"E Lanitis","year":"2025","unstructured":"Lanitis E, Irving M, Coukos G (2025) Tumour-associated vasculature in T cell homing and immunity: opportunities for cancer therapy. Nat Rev Immunol. https:\/\/doi.org\/10.1038\/s41577-025-01187-w","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"10042_CR4","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1158\/0008-5472.CAN-15-1150","volume":"76","author":"DM Corey","year":"2016","unstructured":"Corey DM, Rinkevich Y, Weissman IL (2016) Dynamic patterns of clonal evolution in tumor vasculature underlie alterations in lymphocyte-endothelial recognition to foster tumor immune escape. Cancer Res 76(6):1348\u20131353. https:\/\/doi.org\/10.1158\/0008-5472.CAN-15-1150","journal-title":"Cancer Res"},{"issue":"6","key":"10042_CR5","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.ccell.2021.04.014","volume":"39","author":"A Bagaev","year":"2021","unstructured":"Bagaev A, Kotlov N, Nomie K, Svekolkin V, Gafurov A, Isaeva O, Osokin N, Kozlov I, Frenkel F, Gancharova O, Almog N, Tsiper M, Ataullakhanov R, Fowler N (2021) Conserved pan-cancer microenvironment subtypes predict response to immunotherapy. Cancer Cell 39(6):845\u2013865. https:\/\/doi.org\/10.1016\/j.ccell.2021.04.014","journal-title":"Cancer Cell"},{"issue":"6","key":"10042_CR6","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.ccell.2023.04.011","volume":"41","author":"J Li","year":"2023","unstructured":"Li J, Wu C, Hu H, Qin G, Wu X, Bai F, Zhang J, Cai Y, Huang Y, Wang C, Yang J, Luan Y, Jiang Z, Ling J, Wu Z, Chen Y, Xie Z, Deng Y (2023) Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer. Cancer Cell 41(6):1152\u20131169. https:\/\/doi.org\/10.1016\/j.ccell.2023.04.011","journal-title":"Cancer Cell"},{"issue":"10","key":"10042_CR7","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1158\/2326-6066.CIR-20-0983","volume":"9","author":"FS Hodi","year":"2021","unstructured":"Hodi FS, Wolchok JD, Schadendorf D, Larkin J, Long GV, Qian X, Saci A, Young TC, Srinivasan S, Chang H, Tang H, Wind-Rotolo M, Rizzo JI, Jackson DG, Ascierto PA (2021) TMB and inflammatory gene expression associated with clinical outcomes following immunotherapy in advanced melanoma. Cancer Immunol Res 9(10):1202\u20131213. https:\/\/doi.org\/10.1158\/2326-6066.CIR-20-0983","journal-title":"Cancer Immunol Res"},{"issue":"1","key":"10042_CR8","doi-asserted-by":"publisher","first-page":"5914","DOI":"10.1038\/s41467-023-40994-4","volume":"14","author":"TMR Noviello","year":"2023","unstructured":"Noviello TMR, Di Giacomo AM, Caruso FP, Covre A, Mortarini R, Scala G, Costa MC, Coral S, Fridman WH, Saut\u00e8s-Fridman C, Brich S, Pruneri G, Simonetti E, Lofiego MF, Tufano R, Bedognetti D, Anichini A, Maio M, Ceccarelli M (2023) Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial. Nat Commun 14(1):5914\u20135914. https:\/\/doi.org\/10.1038\/s41467-023-40994-4","journal-title":"Nat Commun"},{"issue":"3","key":"10042_CR9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41568-019-0109-9","volume":"19","author":"PA Jones","year":"2019","unstructured":"Jones PA, Ohtani H, Chakravarthy A, De Carvalho DD (2019) Epigenetic therapy in immune-oncology. Nat Rev Cancer 19(3):151\u2013161. https:\/\/doi.org\/10.1038\/s41568-019-0109-9","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"10042_CR10","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/s41571-024-00886-y","volume":"21","author":"HY Kuo","year":"2024","unstructured":"Kuo HY, Khan KA, Kerbel RS (2024) Antiangiogenic-immune-checkpoint inhibitor combinations: lessons from phase III clinical trials. Nat Rev Clin Oncol 21(6):468\u2013482. https:\/\/doi.org\/10.1038\/s41571-024-00886-y","journal-title":"Nat Rev Clin Oncol"},{"issue":"5","key":"10042_CR11","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrclinonc.2018.29","volume":"15","author":"D Fukumura","year":"2018","unstructured":"Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK (2018) Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol 15(5):325\u2013340. https:\/\/doi.org\/10.1038\/nrclinonc.2018.29","journal-title":"Nat Rev Clin Oncol"},{"key":"10042_CR12","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aak9670","author":"M Schmittnaegel","year":"2017","unstructured":"Schmittnaegel M, Rigamonti N, Kadioglu E, Cassara A, Wyser Rmili C, Kiialainen A, Kienast Y, Mueller HJ, Ooi CH, Laoui D, De Palma M (2017) Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci Transl Med. https:\/\/doi.org\/10.1126\/scitranslmed.aak9670","journal-title":"Sci Transl Med"},{"issue":"3","key":"10042_CR13","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1172\/JCI129558","volume":"130","author":"S Ragusa","year":"2020","unstructured":"Ragusa S, Prat-Luri B, Gonzalez-Loyola A, Nassiri S, Squadrito ML, Guichard A, Cavin S, Gjorevski N, Barras D, Marra G, Lutolf MP, Perentes J, Corse E, Bianchi R, Wetterwald L, Kim J, Oliver G, Delorenzi M, De Palma M, Petrova TV (2020) Antiangiogenic immunotherapy suppresses desmoplastic and chemoresistant intestinal tumors in mice. J Clin Invest 130(3):1199\u20131216. https:\/\/doi.org\/10.1172\/JCI129558","journal-title":"J Clin Invest"},{"issue":"12","key":"10042_CR14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2424730122","volume":"122","author":"EJM Huijbers","year":"2025","unstructured":"Huijbers EJM, van Beijnum JR, van Loon K, Griffioen CJ, Volckmann R, Bassez A, Lambrechts D, Nunes Monteiro M, Jimenez CR, Hogendoorn PCW, Koster J, Griffioen AW (2025) Embryonic reprogramming of the tumor vasculature reveals targets for cancer therapy. Proc Natl Acad Sci U S A 122(12):e2424730122. https:\/\/doi.org\/10.1073\/pnas.2424730122","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"10042_CR15","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.trecan.2017.10.002","volume":"3","author":"M Schmittnaegel","year":"2017","unstructured":"Schmittnaegel M, De Palma M (2017) Reprogramming tumor blood vessels for enhancing immunotherapy. Trends Cancer 3(12):809\u2013812. https:\/\/doi.org\/10.1016\/j.trecan.2017.10.002","journal-title":"Trends Cancer"},{"issue":"3","key":"10042_CR16","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s10456-024-09913-z","volume":"27","author":"F Yang","year":"2024","unstructured":"Yang F, Lee G, Fan Y (2024) Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism. Angiogenesis 27(3):333\u2013349. https:\/\/doi.org\/10.1007\/s10456-024-09913-z","journal-title":"Angiogenesis"},{"key":"10042_CR17","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/bs.acr.2015.05.001","volume":"128","author":"JD Peske","year":"2015","unstructured":"Peske JD, Woods AB, Engelhard VH (2015) Control of CD8 T-cell infiltration into tumors by vasculature and microenvironment. Adv Cancer Res 128:263\u2013307. https:\/\/doi.org\/10.1016\/bs.acr.2015.05.001","journal-title":"Adv Cancer Res"},{"key":"10042_CR18","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aak9679","author":"E Allen","year":"2017","unstructured":"Allen E, Jabouille A, Rivera LB, Lodewijckx I, Missiaen R, Steri V, Feyen K, Tawney J, Hanahan D, Michael IP, Bergers G (2017) Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med. https:\/\/doi.org\/10.1126\/scitranslmed.aak9679","journal-title":"Sci Transl Med"},{"issue":"1","key":"10042_CR19","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.ccell.2022.12.006","volume":"41","author":"Y Hua","year":"2023","unstructured":"Hua Y, Vella G, Rambow F, Allen E, Martinez AA, Duhamel M, Takeda A, Jalkanen S, Junius S, Smeets A, Nittner D, Dimmeler S, Hehlgans T, Liston A, Bosisio FM, Floris G, Laoui D, Hollmen M, Lambrechts D, Merchiers P, Marine JC, Schlenner S, Bergers G (2023) Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1(+) T lymphocyte niches through a feed-forward loop. Cancer Cell 41(1):226. https:\/\/doi.org\/10.1016\/j.ccell.2022.12.006","journal-title":"Cancer Cell"},{"issue":"6","key":"10042_CR20","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1016\/j.ccell.2023.04.010","volume":"41","author":"M Ramachandran","year":"2023","unstructured":"Ramachandran M, Vaccaro A, van de Walle T, Georganaki M, Lugano R, Vemuri K, Kourougkiaouri D, Vazaios K, Hedlund M, Tsaridou G, Uhrbom L, Pietila I, Martikainen M, van Hooren L, Olsson Bontell T, Jakola AS, Yu D, Westermark B, Essand M, Dimberg A (2023) Tailoring vascular phenotype through AAV therapy promotes anti-tumor immunity in glioma. Cancer Cell 41(6):1134\u20131151. https:\/\/doi.org\/10.1016\/j.ccell.2023.04.010","journal-title":"Cancer Cell"},{"issue":"12","key":"10042_CR21","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202318028","volume":"15","author":"J Verhoeven","year":"2023","unstructured":"Verhoeven J, Jacobs KA, Rizzollo F, Lodi F, Hua Y, Pozniak J, Narayanan Srinivasan A, Houbaert D, Shankar G, More S, Schaaf MB, Dubroja Lakic N, Ganne M, Lamote J, Van Weyenbergh J, Boon L, Bechter O, Bosisio F, Uchiyama Y, Bertrand MJ, Marine JC, Lambrechts D, Bergers G, Agrawal M, Agostinis P (2023) Tumor endothelial cell autophagy is a key vascular-immune checkpoint in melanoma. EMBO Mol Med 15(12):e18028. https:\/\/doi.org\/10.15252\/emmm.202318028","journal-title":"EMBO Mol Med"},{"issue":"1","key":"10042_CR22","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s43018-020-00147-8","volume":"2","author":"W Ma","year":"2021","unstructured":"Ma W, Wang Y, Zhang R, Yang F, Zhang D, Huang M, Zhang L, Dorsey JF, Binder ZA, O\u2019Rourke DM, Fraietta JA, Gong Y, Fan Y (2021) Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma. Nat Cancer 2(1):83\u201397. https:\/\/doi.org\/10.1038\/s43018-020-00147-8","journal-title":"Nat Cancer"},{"issue":"9","key":"10042_CR23","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41577-022-00694-4","volume":"22","author":"J Amersfoort","year":"2022","unstructured":"Amersfoort J, Eelen G, Carmeliet P (2022) Immunomodulation by endothelial cells - partnering up with the immune system? Nat Rev Immunol 22(9):576\u2013588. https:\/\/doi.org\/10.1038\/s41577-022-00694-4","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"10042_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62399-1","volume":"16","author":"Y Zhu","year":"2025","unstructured":"Zhu Y, Brulois KF, Dinh TT, Pan J, Butcher EC (2025) COUP-TFII-mediated reprogramming of the vascular endothelium counteracts tumor immune evasion. Nat Commun 16(1):7457. https:\/\/doi.org\/10.1038\/s41467-025-62399-1","journal-title":"Nat Commun"},{"key":"10042_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37807-z","author":"DJ Kim","year":"2023","unstructured":"Kim DJ, Anandh S, Null JL, Przanowski P, Bhatnagar S, Kumar P, Shelton SE, Grundy EE, Chiappinelli KB, Kamm RD, Barbie DA, Dudley AC (2023) Priming a vascular-selective cytokine response permits CD8+ T-cell entry into tumors. Nat Commun. https:\/\/doi.org\/10.1038\/s41467-023-37807-z","journal-title":"Nat Commun"},{"issue":"1","key":"10042_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37807-z","volume":"14","author":"DJ Kim","year":"2023","unstructured":"Kim DJ, Anandh S, Null JL, Przanowski P, Bhatnagar S, Kumar P, Shelton SE, Grundy EE, Chiappinelli KB, Kamm RD, Barbie DA, Dudley AC (2023) Priming a vascular-selective cytokine response permits CD8(+) T-cell entry into tumors. Nat Commun 14(1):2122","journal-title":"Nat Commun"},{"issue":"4","key":"10042_CR27","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/pcmr.12591","volume":"30","author":"J Wang","year":"2017","unstructured":"Wang J, Perry CJ, Meeth K, Thakral D, Damsky W, Micevic G, Kaech S, Blenman K, Bosenberg M (2017) UV-induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell Melanoma Res 30(4):428\u2013435. https:\/\/doi.org\/10.1111\/pcmr.12591","journal-title":"Pigment Cell Melanoma Res"},{"issue":"10","key":"10042_CR28","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1038\/s41592-025-02824-x","volume":"22","author":"C Yapp","year":"2025","unstructured":"Yapp C, Nirmal AJ, Zhou F, Wong AYH, Tefft JB, Lu YD, Shang Z, Maliga Z, Llopis PM, Murphy GF, Lian CG, Danuser G, Santagata S, Sorger PK (2025) Highly multiplexed 3D profiling of cell states and immune niches in human tumors. Nat Methods 22(10):2180\u20132193. https:\/\/doi.org\/10.1038\/s41592-025-02824-x","journal-title":"Nat Methods"},{"issue":"51","key":"10042_CR29","doi-asserted-by":"publisher","first-page":"E10981","DOI":"10.1073\/pnas.1712514114","volume":"114","author":"ML Stone","year":"2017","unstructured":"Stone ML, Chiappinelli KB, Li H, Murphy LM, Travers ME, Topper MJ, Mathios D, Lim M, Shih IM, Wang TL, Hung CF, Bhargava V, Wiehagen KR, Cowley GS, Bachman KE, Strick R, Strissel PL, Baylin SB, Zahnow CA (2017) Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. Proc Natl Acad Sci U S A 114(51):E10981\u2013E10990. https:\/\/doi.org\/10.1073\/pnas.1712514114","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"10042_CR30","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.cell.2017.03.036","volume":"169","author":"KB Chiappinelli","year":"2017","unstructured":"Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, Hein A, Rote NS, Cope LM, Snyder A, Makarov V, Budhu S, Slamon DJ, Wolchok JD, Pardoll DM, Beckmann MW, Zahnow CA, Merghoub T, Chan TA, Baylin SB, Strick R (2017) Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 169(2):361. https:\/\/doi.org\/10.1016\/j.cell.2017.03.036","journal-title":"Cell"},{"issue":"3","key":"10042_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.002","volume":"37","author":"J Goveia","year":"2020","unstructured":"Goveia J, Rohlenova K, Taverna F, Treps L, Conradi LC, Pircher A, Geldhof V, de Rooij L, Kalucka J, Sokol L, Garcia-Caballero M, Zheng Y, Qian J, Teuwen LA, Khan S, Boeckx B, Wauters E, Decaluwe H, De Leyn P, Vansteenkiste J, Weynand B, Sagaert X, Verbeken E, Wolthuis A, Topal B, Everaerts W, Bohnenberger H, Emmert A, Panovska D, De Smet F, Staal FJT, McLaughlin RJ, Impens F, Lagani V, Vinckier S, Mazzone M, Schoonjans L, Dewerchin M, Eelen G, Karakach TK, Yang H, Wang J, Bolund L, Lin L, Thienpont B, Li X, Lambrechts D, Luo Y, Carmeliet P (2020) An integrated gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates. Cancer Cell 37(3):421. https:\/\/doi.org\/10.1016\/j.ccell.2020.03.002","journal-title":"Cancer Cell"},{"issue":"1","key":"10042_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8114","volume":"6","author":"JD Peske","year":"2015","unstructured":"Peske JD, Thompson ED, Gemta L, Baylis RA, Fu Y-X, Engelhard VH (2015) Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity. Nat Commun 6(1):7114. https:\/\/doi.org\/10.1038\/ncomms8114","journal-title":"Nat Commun"},{"key":"10042_CR33","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041170","author":"P Alcaide","year":"2022","unstructured":"Alcaide P (2022) Mechanisms regulating T cell-endothelial cell interactions. Cold Spring Harb Perspect Med. https:\/\/doi.org\/10.1101\/cshperspect.a041170","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"22","key":"10042_CR34","doi-asserted-by":"publisher","first-page":"10770","DOI":"10.1158\/0008-5472.CAN-06-1609","volume":"66","author":"DM Hellebrekers","year":"2006","unstructured":"Hellebrekers DM, Castermans K, Vire E, Dings RP, Hoebers NT, Mayo KH, Oude Egbrink MG, Molema G, Fuks F, van Engeland M, Griffioen AW (2006) Epigenetic regulation of tumor endothelial cell anergy: silencing of intercellular adhesion molecule-1 by histone modifications. Cancer Res 66(22):10770\u201310777. https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-1609","journal-title":"Cancer Res"},{"issue":"9","key":"10042_CR35","doi-asserted-by":"publisher","first-page":"4138","DOI":"10.1158\/0008-5472.CAN-06-3032","volume":"67","author":"DM Hellebrekers","year":"2007","unstructured":"Hellebrekers DM, Melotte V, Vire E, Langenkamp E, Molema G, Fuks F, Herman JG, Van Criekinge W, Griffioen AW, van Engeland M (2007) Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res 67(9):4138\u20134148. https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-3032","journal-title":"Cancer Res"},{"issue":"11","key":"10042_CR36","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/nri3908","volume":"15","author":"D Vestweber","year":"2015","unstructured":"Vestweber D (2015) How leukocytes cross the vascular endothelium. Nat Rev Immunol 15(11):692\u2013704. https:\/\/doi.org\/10.1038\/nri3908","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"10042_CR37","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1158\/2326-6066.CIR-17-0190","volume":"5","author":"AN Woods","year":"2017","unstructured":"Woods AN, Wilson AL, Srivinisan N, Zeng J, Dutta AB, Peske JD, Tewalt EF, Gregg RK, Ferguson AR, Engelhard VH (2017) Differential expression of homing receptor ligands on tumor-associated vasculature that control CD8 effector T-cell entry. Cancer Immunol Res 5(12):1062\u20131073. https:\/\/doi.org\/10.1158\/2326-6066.CIR-17-0190","journal-title":"Cancer Immunol Res"},{"issue":"8","key":"10042_CR38","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41571-021-00496-y","volume":"18","author":"ZR Huinen","year":"2021","unstructured":"Huinen ZR, Huijbers EJM, van Beijnum JR, Nowak-Sliwinska P, Griffioen AW (2021) Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol 18(8):527\u2013540. https:\/\/doi.org\/10.1038\/s41571-021-00496-y","journal-title":"Nat Rev Clin Oncol"},{"issue":"10","key":"10042_CR39","doi-asserted-by":"publisher","first-page":"4350","DOI":"10.1172\/JCI125413","volume":"129","author":"H Yang","year":"2019","unstructured":"Yang H, Lee WS, Kong SJ, Kim CG, Kim JH, Chang SK, Kim S, Kim G, Chon HJ, Kim C (2019) STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade. J Clin Invest 129(10):4350\u20134364. https:\/\/doi.org\/10.1172\/JCI125413","journal-title":"J Clin Invest"},{"issue":"2","key":"10042_CR40","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.molmed.2023.11.002","volume":"30","author":"AH Cleveland","year":"2024","unstructured":"Cleveland AH, Fan Y (2024) Reprogramming endothelial cells to empower cancer immunotherapy. Trends Mol Med 30(2):126\u2013135. https:\/\/doi.org\/10.1016\/j.molmed.2023.11.002","journal-title":"Trends Mol Med"},{"issue":"83","key":"10042_CR41","doi-asserted-by":"publisher","first-page":"eadd1153","DOI":"10.1126\/sciimmunol.add1153","volume":"8","author":"L Wang-Bishop","year":"2023","unstructured":"Wang-Bishop L, Kimmel BR, Ngwa VM, Madden MZ, Baljon JJ, Florian DC, Hanna A, Pastora LE, Sheehy TL, Kwiatkowski AJ, Wehbe M, Wen X, Becker KW, Garland KM, Schulman JA, Shae D, Edwards D, Wolf MM, Delapp R, Christov PP, Beckermann KE, Balko JM, Rathmell WK, Rathmell JC, Chen J, Wilson JT (2023) STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy. Sci Immunol 8(83):eadd1153. https:\/\/doi.org\/10.1126\/sciimmunol.add1153","journal-title":"Sci Immunol"},{"issue":"6","key":"10042_CR42","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1161\/CIRCRESAHA.125.326145","volume":"137","author":"LS Tombor","year":"2025","unstructured":"Tombor LS, Lautenschlager T, Glaser SF, Fischer A, Merten M, Hille SS, Muller OJ, Kupatt C, Bozoglu T, Kugler C, Sami H, Ogris M, Stilz KA, Panthel J, Muhly-Reinholz M, Kettenhausen LM, Zanders L, Stein L, Kiessling P, Sicklinger F, Leuschner F, Schuhmacher B, Siragusa M, Rodriguez Morales D, John D, Kujundzic H, Katschke MT, Solomonidis EG, Luxan G, Hehlgans S, Rodel F, Kuppe C, Abplanalp WT, Cremer S, Dimmeler S (2025) Immunoregulatory endothelial cells interact with T cells after myocardial infarction. Circ Res 137(6):866\u2013879. https:\/\/doi.org\/10.1161\/CIRCRESAHA.125.326145","journal-title":"Circ Res"},{"issue":"10","key":"10042_CR43","doi-asserted-by":"publisher","first-page":"107937","DOI":"10.1016\/j.isci.2023.107937","volume":"26","author":"SL Freshour","year":"2023","unstructured":"Freshour SL, Chen TH, Fisk B, Shen H, Mosior M, Skidmore ZL, Fronick C, Bolzenius JK, Griffith OL, Arora VK, Griffith M (2023) Endothelial cells are a key target of IFN-g during response to combined PD-1\/CTLA-4 ICB treatment in a mouse model of bladder cancer. iScience 26(10):107937. https:\/\/doi.org\/10.1016\/j.isci.2023.107937","journal-title":"iScience"},{"key":"10042_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-025-00563-4","author":"M Stamataki","year":"2025","unstructured":"Stamataki M, Luschow J, Schlumbohm C, Alawi M, Lunding L, Fuchs E, Trepel M, Schwaninger M, Korbelin J (2025) Identification of AAV variants with improved transduction of human vascular endothelial cells by screening AAV capsid libraries in non-human primates. Gene Ther. https:\/\/doi.org\/10.1038\/s41434-025-00563-4","journal-title":"Gene Ther"},{"key":"10042_CR45","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3348","author":"A Cachot","year":"2021","unstructured":"Cachot A, Bilous M, Liu YC, Li X, Saillard M, Cenerenti M, Rockinger GA, Wyss T, Guillaume P, Schmidt J, Genolet R, Ercolano G, Protti MP, Reith W, Ioannidou K, de Leval L, Trapani JA, Coukos G, Harari A, Speiser DE, Mathis A, Gfeller D, Altug H, Romero P, Jandus C (2021) Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer. Sci Adv. https:\/\/doi.org\/10.1126\/sciadv.abe3348","journal-title":"Sci Adv"},{"issue":"1","key":"10042_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","volume":"39","author":"DS Chen","year":"2013","unstructured":"Chen DS, Mellman I (2013) Oncology meets immunology: the cancer-immunity cycle. Immunity 39(1):1\u201310. https:\/\/doi.org\/10.1016\/j.immuni.2013.07.012","journal-title":"Immunity"},{"key":"10042_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1291530","volume":"14","author":"C Qian","year":"2023","unstructured":"Qian C, Liu C, Liu W, Zhou R, Zhao L (2023) Targeting vascular normalization: a promising strategy to improve immune-vascular crosstalk in cancer immunotherapy. Front Immunol 14:1291530. https:\/\/doi.org\/10.3389\/fimmu.2023.1291530","journal-title":"Front Immunol"},{"issue":"Pt 2","key":"10042_CR48","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.semcancer.2018.06.002","volume":"52","author":"R Missiaen","year":"2018","unstructured":"Missiaen R, Mazzone M, Bergers G (2018) The reciprocal function and regulation of tumor vessels and immune cells offers new therapeutic opportunities in cancer. Semin Cancer Biol 52(Pt 2):107\u2013116. https:\/\/doi.org\/10.1016\/j.semcancer.2018.06.002","journal-title":"Semin Cancer Biol"},{"issue":"7967","key":"10042_CR49","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41586-023-06199-x","volume":"618","author":"B Kruse","year":"2023","unstructured":"Kruse B, Buzzai AC, Shridhar N, Braun AD, Gellert S, Knauth K, Pozniak J, Peters J, Dittmann P, Mengoni M, van der Sluis TC, Hohn S, Antoranz A, Krone A, Fu Y, Yu D, Essand M, Geffers R, Mougiakakos D, Kahlfuss S, Kashkar H, Gaffal E, Bosisio FM, Bechter O, Rambow F, Marine JC, Kastenmuller W, Muller AJ, Tuting T (2023) CD4(+) T cell-induced inflammatory cell death controls immune-evasive tumours. Nature 618(7967):1033\u20131040. https:\/\/doi.org\/10.1038\/s41586-023-06199-x","journal-title":"Nature"},{"issue":"7","key":"10042_CR50","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1158\/0008-5472.CAN-14-1616","volume":"75","author":"L Xiao","year":"2015","unstructured":"Xiao L, Kim DJ, Davis CL, McCann JV, Dunleavey JM, Vanderlinden AK, Xu N, Pattenden SG, Frye SV, Xu X, Onaitis M, Monaghan-Benson E, Burridge K, Dudley AC (2015) Tumor endothelial cells with distinct patterns of TGFbeta-driven endothelial-to-mesenchymal transition. Cancer Res 75(7):1244\u20131254. https:\/\/doi.org\/10.1158\/0008-5472.CAN-14-1616","journal-title":"Cancer Res"},{"key":"10042_CR51","doi-asserted-by":"publisher","DOI":"10.3791\/53072","volume":"105","author":"L Xiao","year":"2015","unstructured":"Xiao L, McCann JV, Dudley AC (2015) Isolation and culture expansion of tumor-specific endothelial cells. J Vis Exp 105:e53072. https:\/\/doi.org\/10.3791\/53072","journal-title":"J Vis Exp"},{"issue":"4","key":"10042_CR52","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1172\/JCI123106","volume":"129","author":"JV McCann","year":"2019","unstructured":"McCann JV, Xiao L, Kim DJ, Khan OF, Kowalski PS, Anderson DG, Pecot CV, Azam SH, Parker JS, Tsai YS, Wolberg AS, Turner SD, Tatsumi K, Mackman N, Dudley AC (2019) Endothelial miR-30c suppresses tumor growth via inhibition of TGF-beta-induced Serpine1. J Clin Invest 129(4):1654\u20131670. https:\/\/doi.org\/10.1172\/JCI123106","journal-title":"J Clin Invest"},{"issue":"3","key":"10042_CR53","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ccr.2008.06.017","volume":"14","author":"AC Dudley","year":"2008","unstructured":"Dudley AC, Khan ZA, Shih SC, Kang SY, Zwaans BM, Bischoff J, Klagsbrun M (2008) Calcification of multipotent prostate tumor endothelium. Cancer Cell 14(3):201\u2013211. https:\/\/doi.org\/10.1016\/j.ccr.2008.06.017","journal-title":"Cancer Cell"}],"container-title":["Angiogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10456-026-10042-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10456-026-10042-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10456-026-10042-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:30:10Z","timestamp":1779204610000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10456-026-10042-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["10042"],"URL":"https:\/\/doi.org\/10.1007\/s10456-026-10042-y","relation":{},"ISSN":["1573-7209"],"issn-type":[{"value":"1573-7209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]},"assertion":[{"value":"12 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"33"}}