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Proinflammatory activity of VEGF-targeted treatment through reversal of tumor endothelial cell anergy.
Nowak-Sliwinska, Patrycja; van Beijnum, Judy R; Griffioen, Christian J; Huinen, Zowi R; Sopesens, Nadine Grima; Schulz, Ralph; Jenkins, Samir V; Dings, Ruud P M; Groenendijk, Floris H; Huijbers, Elisabeth J M; Thijssen, Victor L J L; Jonasch, Eric; Vyth-Dreese, Florry A; Jordanova, Ekaterina S; Bex, Axel; Bernards, René; de Gruijl, Tanja D; Griffioen, Arjan W.
Afiliación
  • Nowak-Sliwinska P; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands. Patrycja.Nowak-Sliwinska@unige.ch.
  • van Beijnum JR; School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Patrycja Nowak-Sliwinska, Rue Michel-Servet 1, CMU, 1211, Geneva 4, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.
  • Griffioen CJ; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland. Patrycja.Nowak-Sliwinska@unige.ch.
  • Huinen ZR; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Sopesens NG; CimCure BV, Amsterdam, The Netherlands.
  • Schulz R; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Jenkins SV; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Dings RPM; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Groenendijk FH; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Huijbers EJM; Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
  • Thijssen VLJL; Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
  • Jonasch E; Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Vyth-Dreese FA; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Jordanova ES; CimCure BV, Amsterdam, The Netherlands.
  • Bex A; Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  • Bernards R; Department of Genitourinary Oncology, MD Anderson Cancer Center, Houston, TX, USA.
  • de Gruijl TD; Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Griffioen AW; Center for Gynaecologic Oncology Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Angiogenesis ; 26(2): 279-293, 2023 05.
Article en En | MEDLINE | ID: mdl-36459240
PURPOSE: Ongoing angiogenesis renders the tumor endothelium unresponsive to inflammatory cytokines and interferes with adhesion of leukocytes, resulting in escape from immunity. This process is referred to as tumor endothelial cell anergy. We aimed to investigate whether anti-angiogenic agents can overcome endothelial cell anergy and provide pro-inflammatory conditions. EXPERIMENTAL DESIGN: Tissues of renal cell carcinoma (RCC) patients treated with VEGF pathway-targeted drugs and control tissues were subject to RNAseq and immunohistochemical profiling of the leukocyte infiltrate. Analysis of adhesion molecule regulation in cultured endothelial cells, in a preclinical model and in human tissues was performed and correlated to leukocyte infiltration. RESULTS: It is shown that treatment of RCC patients with the drugs sunitinib or bevacizumab overcomes tumor endothelial cell anergy. This treatment resulted in an augmented inflammatory state of the tumor, characterized by enhanced infiltration of all major leukocyte subsets, including T cells, regulatory T cells, macrophages of both M1- and M2-like phenotypes and activated dendritic cells. In vitro, exposure of angiogenic endothelial cells to anti-angiogenic drugs normalized ICAM-1 expression. In addition, a panel of tyrosine kinase inhibitors was shown to increase transendothelial migration of both non-adherent and monocytic leukocytes. In primary tumors of RCC patients, ICAM-1 expression was found to be significantly increased in both the sunitinib and bevacizumab-treated groups. Genomic analysis confirmed the correlation between increased immune cell infiltration and ICAM-1 expression upon VEGF-targeted treatment. CONCLUSION: The results support the emerging concept that anti-angiogenic therapy can boost immunity and show how immunotherapy approaches can benefit from combination with anti-angiogenic compounds.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Inhibidores de la Angiogénesis / Células Endoteliales / Neoplasias Renales / Neovascularización Patológica Idioma: En Revista: Angiogenesis Asunto de la revista: HEMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Inhibidores de la Angiogénesis / Células Endoteliales / Neoplasias Renales / Neovascularización Patológica Idioma: En Revista: Angiogenesis Asunto de la revista: HEMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania