Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression
Dalton, Heather J. y Pradeep, Sunila y McGuire, Michael y Hailemichael, Yared y MA, Shaolin y Lyons, Yasmin y Armaiz Pena, Guillermo N. y Previs, Rebecca A. y Hansen, Jean Marie y Rupaimoole, Rajesha y González Villasana, Vianey y Cho, Min Soon y Wu, Sherry Y. y Mangala, Lingegowda S. y Jennings, Nicholas B. y Hu, Wei y Langley, Robert y Mu, Hong y Andreeff, Michael y Bar Eli, Menashe y Overwijk, Willem y Ram, Prahlad y Lopez Berestein, Gabriel y Coleman, Robert L. y Sood, Anil K. (2017) Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression. Clinical Cancer Research, 23 (22). pp. 7034-7046. ISSN 1078-0432
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Resumen
Abstract Purpose: VEGF-targeted therapies have modest efficacy in cancerpatients, butacquiredresistance iscommon. Themechanisms underlying such resistance are poorly understood. Experimental Design: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance. Results: Using murine cancer models of adaptive resistance to anti-VEGF antibody (AVA), we found a previously unrecognized roleofmacrophagesinsuchresistance.Macrophageswereactively recruited to the tumor microenvironment and were responsible for the emergence of AVA resistance. Depletion of macrophages following emergence of resistance halted tumor growth and prolonged survival of tumor-bearing mice. In a macrophagedeficient mouse model, resistance to AVA failed to develop, but could be induced by injection of macrophages. Downregulation of macrophage VEGFR-1 and VEGFR-3 expression accompanied upregulation of alternative angiogenic pathways, facilitating escape from anti-VEGF therapy. Conclusions: These findings provide a new understanding of the mechanisms underlying the modest efficacy of current antiangiogenesis therapies and identify new opportunities for combinationapproachesforovarianandothercancers. ClinCancerRes; 23(22); 7034–46. �2017 AACR.
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Divisiones: | Medicina | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Usuario depositante: | Lic. Josimar Pulido | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Fecha del depósito: | 30 Abr 2020 01:48 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Última modificación: | 23 Mar 2022 20:19 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
URI: | http://eprints.uanl.mx/id/eprint/17479 |
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