000			03007 am a22003373u 4500
042			_adc
100	1	0	_aMilutinovic, Stefan _eauthor _92511
700	1	0	_aAbe, Jun _eauthor _92512
700	1	0	_aJones, Emma _eauthor _92513
700	1	0	_aKelch, Inken _eauthor _92514
700	1	0	_aSmart, Kathryn _eauthor _92515
700	1	0	_aLauder, Sarah N. _eauthor _92516
700	1	0	_aSomerville, Michelle _eauthor _92517
700	1	0	_aWare, Carl _eauthor _92518
700	1	0	_aGodkin, Andrew _eauthor _92519
700	1	0	_aStein, Jens V. _eauthor _92520
700	1	0	_aBogle, Gib _eauthor _92521
700	1	0	_aGallimore, Awen _eauthor _92522
245	0	0	_aThree-dimensional Imaging Reveals Immune-driven Tumor-associated High Endothelial Venules as a Key Correlate of Tumor Rejection Following Depletion of Regulatory T Cells
260			_bAmerican Association for Cancer Research, _c2022-12-15.
500			_a/pmc/articles/PMC7614106/
500			_a/pubmed/36704666
520			_aHigh endothelial venules (HEV) are specialized post capillary venules that recruit naïve T cells and B cells into secondary lymphoid organs (SLO) such as lymph nodes (LN). Expansion of HEV networks in SLOs occurs following immune activation to support development of an effective immune response. In this study, we used a carcinogen-induced model of fibrosarcoma to examine HEV remodeling after depletion of regulatory T cells (Treg). We used light sheet fluorescence microscopy imaging to visualize entire HEV networks, subsequently applying computational tools to enable topological mapping and extraction of numerical descriptors of the networks. While these analyses revealed profound cancer- and immune-driven alterations to HEV networks within LNs, these changes did not identify successful responses to treatment. The presence of HEV networks within tumors did however clearly distinguish responders from nonresponders. Finally, we show that a successful treatment response is dependent on coupling tumor-associated HEV (TA-HEV) development to T-cell activation implying that T-cell activation acts as the trigger for development of TA-HEVs which subsequently serve to amplify the immune response by facilitating extravasation of T cells into the tumor mass. SIGNIFICANCE: We used three-dimensional imaging methods with computational tools to analyze networks of specialized blood vessels called HEVs in LNs and tumors. By applying these techniques in a mouse model of carcinogen-induced tumors, we could identify network changes after depletion of Tregs.
540			_a© 2022 The Authors; Published by the American Association for Cancer Research
540			_ahttps://creativecommons.org/licenses/by/4.0/This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
546			_aen
690			_aResearch Article _91689
655	7		_aText _2local
786	0		_nCancer Res Commun
856	4	1	_uhttp://dx.doi.org/10.1158/2767-9764.CRC-21-0123 _zConnect to this object online.
999			_c437 _d437