{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T05:37:46Z","timestamp":1793770666816,"version":"4.6.1"},"reference-count":129,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T00:00:00Z","timestamp":1515974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Immunol"],"published-print":{"date-parts":[[2018,3]]},"DOI":"10.1038\/nri.2017.145","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T07:01:32Z","timestamp":1515999692000},"page":"195-203","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":534,"title":["Improving immune\u2013vascular crosstalk for cancer immunotherapy"],"prefix":"10.1038","volume":"18","author":[{"given":"Yuhui","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty Y. S.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles K.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving L.","family":"Weissman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"BFnri2017145_CR1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000386035","volume":"13","author":"FM Burnet","year":"1970","unstructured":"Burnet, F. M. The concept of immunological surveillance. Prog. Exp. Tumor Res. 13, 1\u201327 (1970).","journal-title":"Prog. Exp. Tumor Res."},{"key":"BFnri2017145_CR2","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1136\/bmj.1.5023.841","volume":"1","author":"M Burnet","year":"1957","unstructured":"Burnet, M. Cancer: a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications. Br. Med. J. 1, 841\u2013847 (1957).","journal-title":"Br. Med. J."},{"key":"BFnri2017145_CR3","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/35074122","volume":"410","author":"V Shankaran","year":"2001","unstructured":"Shankaran, V. et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107\u20131111 (2001).","journal-title":"Nature"},{"key":"BFnri2017145_CR4","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1126\/science.1203486","volume":"331","author":"RD Schreiber","year":"2011","unstructured":"Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331, 1565\u20131570 (2011).","journal-title":"Science"},{"key":"BFnri2017145_CR5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrclinonc.2016.25","volume":"13","author":"DN Khalil","year":"2016","unstructured":"Khalil, D. N., Smith, E. L., Brentjens, R. J. & Wolchok, J. D. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat. Rev. Clin. Oncol. 13, 273\u2013290 (2016).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"BFnri2017145_CR6","doi-asserted-by":"crossref","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","volume":"3","author":"M Kalos","year":"2011","unstructured":"Kalos, M. et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci. Transl Med. 3, 95ra73 (2011).","journal-title":"Sci. Transl Med."},{"key":"BFnri2017145_CR7","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1056\/NEJMoa1103849","volume":"365","author":"DL Porter","year":"2011","unstructured":"Porter, D. L., Levine, B. L., Kalos, M., Bagg, A. & June, C. H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365, 725\u2013733 (2011).","journal-title":"N. Engl. J. Med."},{"key":"BFnri2017145_CR8","first-page":"27","volume":"10","author":"Z Eshhar","year":"1990","unstructured":"Eshhar, Z. & Gross, G. Chimeric T cell receptor which incorporates the anti-tumour specificity of a monoclonal antibody with the cytolytic activity of T cells: a model system for immunotherapeutical approach. Br. J. Cancer. Suppl. 10, 27\u201329 (1990).","journal-title":"Br. J. Cancer. Suppl."},{"key":"BFnri2017145_CR9","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1038\/nm1295-1297","volume":"1","author":"JI Mayordomo","year":"1995","unstructured":"Mayordomo, J. I. et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat. Med. 1, 1297\u20131302 (1995).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nm1100","volume":"10","author":"SA Rosenberg","year":"2004","unstructured":"Rosenberg, S. A., Yang, J. C. & Restifo, N. P. Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10, 909\u2013915 (2004).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR11","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/jnci\/djs033","volume":"104","author":"J Schlom","year":"2012","unstructured":"Schlom, J. Therapeutic cancer vaccines: current status and moving forward. J. Natl Cancer Inst. 104, 599\u2013613 (2012).","journal-title":"J. Natl Cancer Inst."},{"key":"BFnri2017145_CR12","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1634\/theoncologist.2010-0129","volume":"15","author":"RA Madan","year":"2010","unstructured":"Madan, R. A., Gulley, J. L., Fojo, T. & Dahut, W. L. Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression. Oncologist 15, 969\u2013975 (2010).","journal-title":"Oncologist"},{"key":"BFnri2017145_CR13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","volume":"12","author":"DM Pardoll","year":"2012","unstructured":"Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252\u2013264 (2012).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnri2017145_CR14","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","volume":"363","author":"FS Hodi","year":"2010","unstructured":"Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711\u2013723 (2010).","journal-title":"N. Engl. J. Med."},{"key":"BFnri2017145_CR15","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","volume":"387","author":"RS Herbst","year":"2016","unstructured":"Herbst, R. S. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387, 1540\u20131550 (2016).","journal-title":"Lancet"},{"key":"BFnri2017145_CR16","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","volume":"375","author":"M Reck","year":"2016","unstructured":"Reck, M. et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 375, 1823\u20131833 (2016).","journal-title":"N. Engl. J. Med."},{"key":"BFnri2017145_CR17","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa1603702","volume":"374","author":"PT Nghiem","year":"2016","unstructured":"Nghiem, P. T. et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N. Engl. J. Med. 374, 2542\u20132552 (2016).","journal-title":"N. Engl. J. Med."},{"key":"BFnri2017145_CR18","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","volume":"373","author":"RJ Motzer","year":"2015","unstructured":"Motzer, R. J. et al. Nivolumab versus everolimus in advanced renal cell carcinoma. N. Engl. J. Med. 373, 1803\u20131813 (2015).","journal-title":"N. Engl. J. Med."},{"key":"BFnri2017145_CR19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2016.12.022","volume":"168","author":"MH Spitzer","year":"2017","unstructured":"Spitzer, M. H. et al. Systemic immunity is required for effective cancer immunotherapy. Cell 168, 487\u2013502 (2017).","journal-title":"Cell"},{"key":"BFnri2017145_CR20","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1002\/eji.200425474","volume":"34","author":"R Ganss","year":"2004","unstructured":"Ganss, R., Arnold, B. & Hammerling, G. J. Mini-review: overcoming tumor-intrinsic resistance to immune effector function. Eur. J. Immunol. 34, 2635\u20132641 (2004).","journal-title":"Eur. J. Immunol."},{"key":"BFnri2017145_CR21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.immuni.2013.07.005","volume":"39","author":"GT Motz","year":"2013","unstructured":"Motz, G. T. & Coukos, G. Deciphering and reversing tumor immune suppression. Immunity 39, 61\u201373 (2013).","journal-title":"Immunity"},{"key":"BFnri2017145_CR22","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1158\/0008-5472.CAN-12-4354","volume":"73","author":"Y Huang","year":"2013","unstructured":"Huang, Y., Goel, S., Duda, D. G., Fukumura, D. & Jain, R. K. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res. 73, 2943\u20132948 (2013).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.coi.2015.01.011","volume":"33","author":"E Lanitis","year":"2015","unstructured":"Lanitis, E., Irving, M. & Coukos, G. Targeting the tumor vasculature to enhance T cell activity. Curr. Opin. Immunol. 33, 55\u201363 (2015).","journal-title":"Curr. Opin. Immunol."},{"key":"BFnri2017145_CR24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/35025220","volume":"407","author":"P Carmeliet","year":"2000","unstructured":"Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407, 249\u2013257 (2000).","journal-title":"Nature"},{"key":"BFnri2017145_CR25","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/359843a0","volume":"359","author":"D Shweiki","year":"1992","unstructured":"Shweiki, D., Itin, A., Soffer, D. & Keshet, E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359, 843\u2013845 (1992).","journal-title":"Nature"},{"key":"BFnri2017145_CR26","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1172\/JCI114759","volume":"86","author":"S Kourembanas","year":"1990","unstructured":"Kourembanas, S., Hannan, R. L. & Faller, D. V. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J. Clin. Invest. 86, 670\u2013674 (1990).","journal-title":"J. Clin. Invest."},{"key":"BFnri2017145_CR27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","volume":"307","author":"RK Jain","year":"2005","unstructured":"Jain, R. K. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307, 58\u201362 (2005).","journal-title":"Science"},{"key":"BFnri2017145_CR28","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ccell.2014.10.006","volume":"26","author":"RK Jain","year":"2014","unstructured":"Jain, R. K. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell 26, 605\u2013622 (2014).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nm1699","volume":"14","author":"RJ Buckanovich","year":"2008","unstructured":"Buckanovich, R. J. et al. Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat. Med. 14, 28\u201336 (2008).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR30","first-page":"4265","volume":"52","author":"NZ Wu","year":"1992","unstructured":"Wu, N. Z., Klitzman, B., Dodge, R. & Dewhirst, M. W. Diminished leukocyte-endothelium interaction in tumor microvessels. Cancer Res. 52, 4265\u20134268 (1992).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR31","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-pathol-011110-130224","volume":"6","author":"WA Muller","year":"2011","unstructured":"Muller, W. A. Mechanisms of leukocyte transendothelial migration. Annu. Rev. Pathol. 6, 323\u2013344 (2011).","journal-title":"Annu. Rev. Pathol."},{"key":"BFnri2017145_CR32","first-page":"1111","volume":"56","author":"AW Griffioen","year":"1996","unstructured":"Griffioen, A. W. et al. Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors. Cancer Res. 56, 1111\u20131117 (1996).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR33","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nri.2017.49","volume":"17","author":"N Nagarsheth","year":"2017","unstructured":"Nagarsheth, N., Wicha, M. S. & Zou, W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat. Rev. Immunol. 17, 559\u2013572 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"BFnri2017145_CR34","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ccell.2016.02.004","volume":"29","author":"H Tang","year":"2016","unstructured":"Tang, H. et al. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell 29, 285\u2013296 (2016).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR35","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.trecan.2016.09.007","volume":"2","author":"W Jiang","year":"2016","unstructured":"Jiang, W., Chan, C. K., Weissman, I. L., Kim, B. Y. S. & Hahn, S. M. Immune priming of the tumor microenvironment by radiation. Trends Cancer 2, 638\u2013645 (2016).","journal-title":"Trends Cancer"},{"key":"BFnri2017145_CR36","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nm.4123","volume":"22","author":"H Jiang","year":"2016","unstructured":"Jiang, H. et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 22, 851\u2013860 (2016).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR37","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/nri.2017.103","volume":"17","author":"CT Taylor","year":"2017","unstructured":"Taylor, C. T. & Colgan, S. P. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat. Rev. Immunol. 17, 774\u2013785 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"BFnri2017145_CR38","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1084\/jem.20100587","volume":"207","author":"CA Corzo","year":"2010","unstructured":"Corzo, C. A. et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 207, 2439\u20132453 (2010).","journal-title":"J. Exp. Med."},{"key":"BFnri2017145_CR39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","volume":"141","author":"BZ Qian","year":"2010","unstructured":"Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39\u201351 (2010).","journal-title":"Cell"},{"key":"BFnri2017145_CR40","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nri3175","volume":"12","author":"DI Gabrilovich","year":"2012","unstructured":"Gabrilovich, D. I., Ostrand-Rosenberg, S. & Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12, 253\u2013268 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"BFnri2017145_CR41","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nm1093","volume":"10","author":"TJ Curiel","year":"2004","unstructured":"Curiel, T. J. et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942\u2013949 (2004).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR42","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nature10169","volume":"475","author":"A Facciabene","year":"2011","unstructured":"Facciabene, A. et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 475, 226\u2013230 (2011).","journal-title":"Nature"},{"key":"BFnri2017145_CR43","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1158\/0008-5472.CAN-10-1439","volume":"70","author":"AL Doedens","year":"2010","unstructured":"Doedens, A. L. et al. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 70, 7465\u20137475 (2010).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR44","doi-asserted-by":"crossref","first-page":"7788","DOI":"10.1158\/0008-5472.CAN-10-1736","volume":"70","author":"K Klages","year":"2010","unstructured":"Klages, K. et al. Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma. Cancer Res. 70, 7788\u20137799 (2010).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR45","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1158\/0008-5472.CAN-13-0992","volume":"74","author":"IB Barsoum","year":"2014","unstructured":"Barsoum, I. B., Smallwood, C. A., Siemens, D. R. & Graham, C. H. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res. 74, 665\u2013674 (2014).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR46","doi-asserted-by":"crossref","first-page":"51210","DOI":"10.18632\/oncotarget.17214","volume":"8","author":"Y Zhou","year":"2017","unstructured":"Zhou, Y. et al. PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma: the correlation with anemia and outcomes. Oncotarget 8, 51210\u201351223 (2017).","journal-title":"Oncotarget"},{"key":"BFnri2017145_CR47","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/ijc.30077","volume":"139","author":"M Ruf","year":"2016","unstructured":"Ruf, M., Moch, H. & Schraml, P. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma. Int. J. Cancer 139, 396\u2013403 (2016).","journal-title":"Int. J. Cancer"},{"key":"BFnri2017145_CR48","doi-asserted-by":"crossref","first-page":"e1108514","DOI":"10.1080\/2162402X.2015.1108514","volume":"5","author":"J Koh","year":"2016","unstructured":"Koh, J. et al. EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1alpha and STAT3. Oncoimmunology 5, e1108514 (2016).","journal-title":"Oncoimmunology"},{"key":"BFnri2017145_CR49","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.1038\/ncomms7340","volume":"6","author":"HS Koh","year":"2015","unstructured":"Koh, H. S. et al. The HIF-1\/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia. Nat. Commun. 6, 6340 (2015).","journal-title":"Nat. Commun."},{"key":"BFnri2017145_CR50","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","volume":"211","author":"MZ Noman","year":"2014","unstructured":"Noman, M. Z. et al. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J. Exp. Med. 211, 781\u2013790 (2014).","journal-title":"J. Exp. Med."},{"key":"BFnri2017145_CR51","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1084\/jem.20140559","volume":"212","author":"T Voron","year":"2015","unstructured":"Voron, T. et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med. 212, 139\u2013148 (2015).","journal-title":"J. Exp. Med."},{"key":"BFnri2017145_CR52","doi-asserted-by":"crossref","first-page":"5947","DOI":"10.1158\/1078-0432.CCR-08-0229","volume":"14","author":"MV Sitkovsky","year":"2008","unstructured":"Sitkovsky, M. V., Kjaergaard, J., Lukashev, D. & Ohta, A. Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells and cancerous tissue hypoxia. Clin. Cancer Res. 14, 5947\u20135952 (2008).","journal-title":"Clin. Cancer Res."},{"key":"BFnri2017145_CR53","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1182\/blood-2006-07-035972","volume":"109","author":"K Fischer","year":"2007","unstructured":"Fischer, K. et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109, 3812\u20133819 (2007).","journal-title":"Blood"},{"key":"BFnri2017145_CR54","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1182\/blood-2005-05-1795","volume":"107","author":"E Gottfried","year":"2006","unstructured":"Gottfried, E. et al. Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood 107, 2013\u20132021 (2006).","journal-title":"Blood"},{"key":"BFnri2017145_CR55","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.semcancer.2017.03.001","volume":"43","author":"V Huber","year":"2017","unstructured":"Huber, V. et al. Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin. Cancer Biol. 43, 74\u201389 (2017).","journal-title":"Semin. Cancer Biol."},{"key":"BFnri2017145_CR56","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/ijc.26410","volume":"131","author":"AN Mendler","year":"2012","unstructured":"Mendler, A. N. et al. Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK\/c-Jun activation. Int. J. Cancer 131, 633\u2013640 (2012).","journal-title":"Int. J. Cancer"},{"key":"BFnri2017145_CR57","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.ccell.2016.10.018","volume":"30","author":"JS Park","year":"2016","unstructured":"Park, J. S. et al. Normalization of tumor vessels by Tie2 activation and Ang2 inhibition enhances drug delivery and produces a favorable tumor microenvironment. Cancer Cell 30, 953\u2013967 (2016).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR58","doi-asserted-by":"crossref","first-page":"8689","DOI":"10.1021\/acsnano.5b02028","volume":"9","author":"W Jiang","year":"2015","unstructured":"Jiang, W., Huang, Y., An, Y. & Kim, B. Y. S. Remodeling tumor vasculature to enhance delivery of intermediate-sized nanoparticles. ACS Nano 9, 8689\u20138696 (2015).","journal-title":"ACS Nano"},{"key":"BFnri2017145_CR59","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/nature06868","volume":"453","author":"J Hamzah","year":"2008","unstructured":"Hamzah, J. et al. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature 453, 410\u2013414 (2008).","journal-title":"Nature"},{"key":"BFnri2017145_CR60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.4049\/jimmunol.172.1.7","volume":"172","author":"Y Liu","year":"2004","unstructured":"Liu, Y. et al. Regulation of leukocyte transmigration: cell surface interactions and signaling events. J. Immunol. 172, 7\u201313 (2004).","journal-title":"J. Immunol."},{"key":"BFnri2017145_CR61","doi-asserted-by":"crossref","first-page":"7144","DOI":"10.1158\/0008-5472.CAN-13-1989","volume":"73","author":"Y Huang","year":"2013","unstructured":"Huang, Y., Stylianopoulos, T., Duda, D. G., Fukumura, D. & Jain, R. K. Benefits of vascular normalization are dose and time dependent. Cancer Res. 73, 7144\u20137146 (2013).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR62","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1158\/0008-5472.CAN-10-0153","volume":"70","author":"RK Shrimali","year":"2010","unstructured":"Shrimali, R. K. et al. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 70, 6171\u20136180 (2010).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR63","doi-asserted-by":"crossref","first-page":"17561","DOI":"10.1073\/pnas.1215397109","volume":"109","author":"Y Huang","year":"2012","unstructured":"Huang, Y. et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc. Natl Acad. Sci. USA 109, 17561\u201317566 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2017145_CR64","doi-asserted-by":"crossref","first-page":"360ra135","DOI":"10.1126\/scitranslmed.aaf5219","volume":"8","author":"NN Rahbari","year":"2016","unstructured":"Rahbari, N. N. et al. Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases. Sci. Transl Med. 8, 360ra135 (2016).","journal-title":"Sci. Transl Med."},{"key":"BFnri2017145_CR65","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1172\/JCI93182","volume":"127","author":"K Jung","year":"2017","unstructured":"Jung, K. et al. Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy. J. Clin. Invest. 127, 3039\u20133051 (2017).","journal-title":"J. Clin. Invest."},{"key":"BFnri2017145_CR66","doi-asserted-by":"crossref","first-page":"277ra30","DOI":"10.1126\/scitranslmed.aaa1260","volume":"7","author":"SM Hatfield","year":"2015","unstructured":"Hatfield, S. M. et al. Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci. Transl Med. 7, 277ra30 (2015).","journal-title":"Sci. Transl Med."},{"key":"BFnri2017145_CR67","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ccr.2011.02.005","volume":"19","author":"R Mazzieri","year":"2011","unstructured":"Mazzieri, R. Targeting the ANG2\/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell 19, 512\u2013526 (2011).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR68","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1158\/0008-5472.CAN-09-1977","volume":"70","author":"H Hashizume","year":"2010","unstructured":"Hashizume, H. et al. Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth. Cancer Res. 70, 2213\u20132223 (2010).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR69","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1073\/pnas.1525349113","volume":"113","author":"TE Peterson","year":"2016","unstructured":"Peterson, T. E. et al. Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages. Proc. Natl Acad. Sci. USA 113, 4470\u20134475 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2017145_CR70","doi-asserted-by":"crossref","first-page":"eaak9670","DOI":"10.1126\/scitranslmed.aak9670","volume":"9","author":"M Schmittnaegel","year":"2017","unstructured":"Schmittnaegel, M. et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci. Transl Med. 9, eaak9670 (2017).","journal-title":"Sci. Transl Med."},{"key":"BFnri2017145_CR71","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1073\/pnas.1525360113","volume":"113","author":"J Kloepper","year":"2016","unstructured":"Kloepper, J. et al. Ang-2\/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival. Proc. Natl Acad. Sci. USA 113, 4476\u20134481 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2017145_CR72","doi-asserted-by":"crossref","first-page":"eaak9679","DOI":"10.1126\/scitranslmed.aak9679","volume":"9","author":"E Allen","year":"2017","unstructured":"Allen, E. et al. Combined antiangiogenic and anti\u2013PD-L1 therapy stimulates tumor immunity through HEV formation. Sci. Transl Med. 9, eaak9679 (2017).","journal-title":"Sci. Transl Med."},{"key":"BFnri2017145_CR73","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.cell.2016.11.022","volume":"167","author":"JL Benci","year":"2016","unstructured":"Benci, J. L. et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell 167, 1540\u20131554 (2016).","journal-title":"Cell"},{"key":"BFnri2017145_CR74","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/ni.3159","volume":"16","author":"R Carretero","year":"2015","unstructured":"Carretero, R. et al. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat. Immunol. 16, 609\u2013617 (2015).","journal-title":"Nat. Immunol."},{"key":"BFnri2017145_CR75","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/nature21724","volume":"544","author":"L Tian","year":"2017","unstructured":"Tian, L. et al. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nature 544, 250\u2013254 (2017).","journal-title":"Nature"},{"key":"BFnri2017145_CR76","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1073\/pnas.0915174107","volume":"107","author":"MA Curran","year":"2010","unstructured":"Curran, M. A., Montalvo, W., Yagita, H. & Allison, J. P. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl Acad. Sci. USA 107, 4275\u20134280 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2017145_CR77","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nm730","volume":"8","author":"H Dong","year":"2002","unstructured":"Dong, H. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793\u2013800 (2002).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR78","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1126\/science.271.5256.1734","volume":"271","author":"DR Leach","year":"1996","unstructured":"Leach, D. R., Krummel, M. F. & Allison, J. P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734\u20131736 (1996).","journal-title":"Science"},{"key":"BFnri2017145_CR79","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nm.4321","volume":"23","author":"CH June","year":"2017","unstructured":"June, C. H., Warshauer, J. T. & Bluestone, J. A. Is autoimmunity the Achilles' heel of cancer immunotherapy? Nat. Med. 23, 540\u2013547 (2017).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR80","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.aaf0683","volume":"355","author":"AO Kamphorst","year":"2017","unstructured":"Kamphorst, A. O. et al. Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science 355, 1423\u20131427 (2017).","journal-title":"Science"},{"key":"BFnri2017145_CR81","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nature22079","volume":"545","author":"AC Huang","year":"2017","unstructured":"Huang, A. C. et al. T-Cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 545, 60\u201365 (2017).","journal-title":"Nature"},{"key":"BFnri2017145_CR82","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nm0498-408","volume":"4","author":"C Ruegg","year":"1998","unstructured":"Ruegg, C. et al. Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. Nat. Med. 4, 408\u2013414 (1998).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR83","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.4049\/jimmunol.166.4.2276","volume":"166","author":"GL Beatty","year":"2001","unstructured":"Beatty, G. L. & Paterson, Y. IFN-\u03b3-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-\u03b3. J. Immunol. 166, 2276\u20132282 (2001).","journal-title":"J. Immunol."},{"key":"BFnri2017145_CR84","first-page":"1728","volume":"100","author":"Y Hayakawa","year":"2002","unstructured":"Hayakawa, Y. et al. IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood 100, 1728\u20131733 (2002).","journal-title":"Blood"},{"key":"BFnri2017145_CR85","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.1182\/blood-2002-07-1956","volume":"101","author":"JE Ohm","year":"2003","unstructured":"Ohm, J. E. et al. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood 101, 4878\u20134886 (2003).","journal-title":"Blood"},{"key":"BFnri2017145_CR86","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/nm1096-1096","volume":"2","author":"DI Gabrilovich","year":"1996","unstructured":"Gabrilovich, D. I. et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med. 2, 1096\u20131103 (1996).","journal-title":"Nat. Med."},{"key":"BFnri2017145_CR87","doi-asserted-by":"crossref","first-page":"6122","DOI":"10.1158\/0008-5472.CAN-10-4366","volume":"71","author":"Y Huang","year":"2011","unstructured":"Huang, Y. et al. Resuscitating cancer immunosurveillance: selective stimulation of DLL1-Notch signaling in T cells rescues T-cell function and inhibits tumor growth. Cancer Res. 71, 6122\u20136131 (2011).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR88","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1182\/blood-2007-01-065714","volume":"110","author":"Y Huang","year":"2007","unstructured":"Huang, Y. et al. Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Blood 110, 624\u2013631 (2007).","journal-title":"Blood"},{"key":"BFnri2017145_CR89","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.it.2004.02.006","volume":"25","author":"P Romagnani","year":"2004","unstructured":"Romagnani, P., Lasagni, L., Annunziato, F., Serio, M. & Romagnani, S. CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol. 25, 201\u2013209 (2004).","journal-title":"Trends Immunol."},{"key":"BFnri2017145_CR90","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1084\/jem.184.3.981","volume":"184","author":"DA Arenberg","year":"1996","unstructured":"Arenberg, D. A. et al. Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J. Exp. Med. 184, 981\u2013992 (1996).","journal-title":"J. Exp. Med."},{"key":"BFnri2017145_CR91","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4049\/jimmunol.164.1.217","volume":"164","author":"HM Fathallah-Shaykh","year":"2000","unstructured":"Fathallah-Shaykh, H. M., Zhao, L. J., Kafrouni, A. I., Smith, G. M. & Forman, J. Gene transfer of IFN-gamma into established brain tumors represses growth by antiangiogenesis. J. Immunol. 164, 217\u2013222 (2000).","journal-title":"J. Immunol."},{"key":"BFnri2017145_CR92","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nature22311","volume":"545","author":"T Kammertoens","year":"2017","unstructured":"Kammertoens, T. et al. Tumour ischaemia by interferon-gamma resembles physiological blood vessel regression. Nature 545, 98\u2013102 (2017).","journal-title":"Nature"},{"key":"BFnri2017145_CR93","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrc.2017.51","volume":"17","author":"M De Palma","year":"2017","unstructured":"De Palma, M., Biziato, D. & Petrova, T. V. Microenvironmental regulation of tumour angiogenesis. Nat. Rev. Cancer 17, 457\u2013474 (2017).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnri2017145_CR94","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature15520","volume":"527","author":"D Peng","year":"2015","unstructured":"Peng, D. et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature 527, 249\u2013253 (2015).","journal-title":"Nature"},{"key":"BFnri2017145_CR95","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature14404","volume":"523","author":"S Spranger","year":"2015","unstructured":"Spranger, S., Bao, R. & Gajewski, T. F. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 523, 231\u2013235 (2015).","journal-title":"Nature"},{"key":"BFnri2017145_CR96","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/nrc2444","volume":"8","author":"C Murdoch","year":"2008","unstructured":"Murdoch, C., Muthana, M., Coffelt, S. B. & Lewis, C. E. The role of myeloid cells in the promotion of tumour angiogenesis. Nat. Rev. Cancer 8, 618\u2013631 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnri2017145_CR97","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ccr.2004.08.031","volume":"6","author":"L Yang","year":"2004","unstructured":"Yang, L. et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6, 409\u2013421 (2004).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR98","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ccell.2016.05.017","volume":"30","author":"CE Lewis","year":"2016","unstructured":"Lewis, C. E., Harney, A. S. & Pollard, J. W. The multifaceted role of perivascular macrophages in tumors. Cancer Cell 30, 18\u201325 (2016).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR99","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cell.2010.03.015","volume":"141","author":"K Kessenbrock","year":"2010","unstructured":"Kessenbrock, K., Plaks, V. & Werb, Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141, 52\u201367 (2010).","journal-title":"Cell"},{"key":"BFnri2017145_CR100","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/jnci\/94.15.1134","volume":"94","author":"S Huang","year":"2002","unstructured":"Huang, S. et al. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J. Natl Cancer Inst. 94, 1134\u20131142 (2002).","journal-title":"J. Natl Cancer Inst."},{"key":"BFnri2017145_CR101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccr.2011.01.005","volume":"19","author":"Y Huang","year":"2011","unstructured":"Huang, Y., Snuderl, M. & Jain, R. K. Polarization of tumor-associated macrophages: a novel strategy for vascular normalization and antitumor immunity. Cancer Cell 19, 1\u20132 (2011).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR102","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ccr.2010.11.009","volume":"19","author":"C Rolny","year":"2011","unstructured":"Rolny, C. et al. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell 19, 31\u201344 (2011).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR103","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrclinonc.2017.88","volume":"14","author":"M Nishino","year":"2017","unstructured":"Nishino, M., Ramaiya, N. H., Hatabu, H. & Hodi, F. S. Monitoring immune-checkpoint blockade: response evaluation and biomarker development. Nat. Rev. Clin. Oncol. 14, 655\u2013668 (2017).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"BFnri2017145_CR104","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.celrep.2014.06.059","volume":"8","author":"N Rigamonti","year":"2014","unstructured":"Rigamonti, N. et al. Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade. Cell Rep. 8, 696\u2013706 (2014).","journal-title":"Cell Rep."},{"key":"BFnri2017145_CR105","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/sj.bjc.6605925","volume":"103","author":"V Goede","year":"2010","unstructured":"Goede, V. et al. Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy. Br. J. Can. 103, 1407\u20131414 (2010).","journal-title":"Br. J. Can."},{"key":"BFnri2017145_CR106","doi-asserted-by":"crossref","first-page":"5226","DOI":"10.1158\/1078-0432.CCR-10-0171","volume":"17","author":"M De Palma","year":"2011","unstructured":"De Palma, M. & Naldini, L. Angiopoietin-2 TIEs up macrophages in tumour angiogenesis. Clin. Cancer Res. 17, 5226\u20135232 (2011).","journal-title":"Clin. Cancer Res."},{"key":"BFnri2017145_CR107","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1158\/2326-6066.CIR-16-0206","volume":"5","author":"W Wu","year":"2017","unstructured":"Wu, W. et al. Angiopoietin-2 as a biomarker and target for immune checkpoint therapy. Can. Immunol. Res. 5, 17\u201328 (2017).","journal-title":"Can. Immunol. Res."},{"key":"BFnri2017145_CR108","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1158\/1078-0432.CCR-14-1956","volume":"21","author":"M Piesche","year":"2015","unstructured":"Piesche, M. et al. Angiogenic cytokines are antibody targets during graft-versus-leukemia reactions. Clin. Cancer Res. 21, 1010\u20131018 (2015).","journal-title":"Clin. Cancer Res."},{"key":"BFnri2017145_CR109","doi-asserted-by":"crossref","first-page":"10150","DOI":"10.1158\/0008-5472.CAN-10-1852","volume":"70","author":"J Schoenfeld","year":"2010","unstructured":"Schoenfeld, J. et al. Active immunotherapy induces antibody responses that target tumor angiogenesis. Cancer Res. 70, 10150\u201310160 (2010).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR110","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1470-2045(06)71012-9","volume":"8","author":"MA Zahra","year":"2007","unstructured":"Zahra, M. A. et al. Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy. Lancet Oncol. 8, 63\u201374 (2007).","journal-title":"Lancet Oncol."},{"key":"BFnri2017145_CR111","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1148\/radiol.10091760","volume":"256","author":"AR Padhani","year":"2010","unstructured":"Padhani, A. R. & Miles, K. A. Multiparametric imaging of tumor response to therapy. Radiology 256, 348\u2013364 (2010).","journal-title":"Radiology"},{"key":"BFnri2017145_CR112","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1158\/0008-5472.CAN-11-0431","volume":"71","author":"L Martinet","year":"2011","unstructured":"Martinet, L. et al. Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res. 71, 5678\u20135687 (2011).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR113","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature14292","volume":"520","author":"C Twyman-Saint Victor","year":"2015","unstructured":"Twyman-Saint Victor, C. et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520, 373\u2013377 (2015).","journal-title":"Nature"},{"key":"BFnri2017145_CR114","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrc3237","volume":"12","author":"M Vanneman","year":"2012","unstructured":"Vanneman, M. & Dranoff, G. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 12, 237\u2013251 (2012).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnri2017145_CR115","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nrc.2017.17","volume":"17","author":"P Gotwals","year":"2017","unstructured":"Gotwals, P. et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat. Rev. Cancer 17, 286\u2013301 (2017).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnri2017145_CR116","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40425-016-0156-7","volume":"4","author":"J Kang","year":"2016","unstructured":"Kang, J., Demaria, S. & Formenti, S. Current clinical trials testing the combination of immunotherapy with radiotherapy. J. Immunother. Cancer 4, 51\u201370 (2016).","journal-title":"J. Immunother. Cancer"},{"key":"BFnri2017145_CR117","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/nrclinonc.2016.30","volume":"13","author":"MB Bernstein","year":"2016","unstructured":"Bernstein, M. B., Krishnan, S., Hodge, J. W. & Chang, J. Y. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat. Rev. Clin. Oncol. 13, 516\u2013524 (2016).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"BFnri2017145_CR118","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.trecan.2016.05.002","volume":"2","author":"S Demaria","year":"2016","unstructured":"Demaria, S., Coleman, C. N. & Formenti, S. C. Radiotherapy: changing the game in immunotherapy. Trends Cancer 2, 286\u2013294 (2016).","journal-title":"Trends Cancer"},{"key":"BFnri2017145_CR119","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.ccr.2013.09.014","volume":"24","author":"F Klug","year":"2013","unstructured":"Klug, F. et al. Low-dose irradiation programs macrophage differentiation to an iNOS+\/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 24, 589\u2013602 (2013).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR120","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ccr.2013.10.019","volume":"24","author":"M De Palma","year":"2013","unstructured":"De Palma, M., Coukos, G. & Hanahan, D. A new twist on radiation oncology: low-dose irradiation elicits immunostimulatory macrophages that unlock barriers to tumor immunotherapy. Cancer Cell 24, 559\u2013561 (2013).","journal-title":"Cancer Cell"},{"key":"BFnri2017145_CR121","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1158\/1078-0432.CCR-14-2824","volume":"21","author":"A Filatenkov","year":"2015","unstructured":"Filatenkov, A. et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin. Cancer Res. 21, 3727\u20133739 (2015).","journal-title":"Clin. Cancer Res."},{"key":"BFnri2017145_CR122","doi-asserted-by":"crossref","first-page":"18632","DOI":"10.1073\/pnas.1318415110","volume":"110","author":"T Stylianopoulosa","year":"2013","unstructured":"Stylianopoulosa, T. & Jain, R. K. Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc. Natl Acad. Sci. USA 110, 18632\u201318637 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2017145_CR123","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1158\/0008-5472.CAN-06-4102","volume":"67","author":"RK Jain","year":"2007","unstructured":"Jain, R. K., Tong, R. T. & Munn, L. L. Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: Insights from a mathematical model. Cancer Res. 67, 2729\u20132735 (2007).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR124","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.trecan.2016.09.005","volume":"2","author":"AW Lund","year":"2016","unstructured":"Lund, A. W. Rethinking lymphatic vessels and antitumor immunity. Trends Cancer 2, 548\u2013551 (2016).","journal-title":"Trends Cancer"},{"key":"BFnri2017145_CR125","first-page":"2821","volume":"46","author":"D Rotin","year":"1986","unstructured":"Rotin, D., Robinson, B. & Tannock, I. F. Influence of hypoxia and an acidic environment on the metabolism and viability of cultured cells: potential implications for cell death in tumors. Cancer Res. 46, 2821\u20132826 (1986).","journal-title":"Cancer Res."},{"key":"BFnri2017145_CR126","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nature19364","volume":"537","author":"R Eil","year":"2016","unstructured":"Eil, R. et al. Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature 537, 539\u2013543 (2016).","journal-title":"Nature"},{"key":"BFnri2017145_CR127","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/ni.3868","volume":"18","author":"T Maj","year":"2017","unstructured":"Maj, T. et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumour. Nat. Immunol. 18, 1332\u20131341 (2017).","journal-title":"Nat. Immunol."},{"key":"BFnri2017145_CR128","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.canlet.2015.10.009","volume":"370","author":"H Tang","year":"2016","unstructured":"Tang, H., Qiao, J. & Fu, Y. X. Immunotherapy and tumor microenvironment. Cancer Lett. 370, 85\u201390 (2016).","journal-title":"Cancer Lett."},{"key":"BFnri2017145_CR129","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/ni.2714","volume":"4","author":"AL Doedens","year":"2013","unstructured":"Doedens, A. L. et al. Hypoxia-inducible factors enhance the effector responses of CD8+ T cells to persistent antigen. Nat. Immunol. 4, 1173\u20131182 (2013).","journal-title":"Nat. Immunol."}],"container-title":["Nature Reviews Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nri.2017.145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nri.2017.145","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nri.2017.145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nri.2017.145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T04:01:41Z","timestamp":1684468901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nri.2017.145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,15]]},"references-count":129,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["BFnri2017145"],"URL":"https:\/\/doi.org\/10.1038\/nri.2017.145","relation":{},"ISSN":["1474-1733","1474-1741"],"issn-type":[{"value":"1474-1733","type":"print"},{"value":"1474-1741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,15]]},"assertion":[{"value":"15 January 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}