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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Microambiente tumoral > DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista >

Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes
Authors: Palazon, A. (Asís)
Teijeira, A. (Álvaro)
Martinez-Forero, I. (Iván)
Hervas-Stubbs, S. (Sandra)
Roncal, C. (Carmen)
Peñuelas, I. (Iván)
Dubrot, J. (Juan)
Morales-Kastresana, A. (Aizea)
Perez-Gracia, J.L. (José Luis)
Ochoa, M.C. (María Carmen)
Ochoa, L. (Laura)
Martinez, A. (Alfredo)
Luque, A. (Alfonso)
Dinchuk, J. (Joseph)
Rouzaut, A. (Ana)
Jure-Kunkel, M. (María)
Melero, I. (Ignacio)
Keywords: Antibodies, Monoclonal/pharmacology
Antigens, CD137/agonists
Endothelial Cells/drug effects
T-Lymphocytes/immunology
Issue Date: 2011
Publisher: American Association for Cancer Research
Publisher version: http://cancerres.aacrjournals.org/content/71/3/801
ISSN: 1538-7445
Citation: Palazon A, Teijeira A, Martinez-Forero I, Hervas-Stubbs S, Roncal C, Penuelas I, et al. Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Cancer Res 2011 Feb 1;71(3):801-811.
Abstract
Agonist monoclonal antibodies (mAb) to the immune costimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment on the basis of their costimulatory effects on primed T cells and perhaps other cells of the immune system. Here we provide evidence that CD137 is selectively expressed on the surface of tumor endothelial cells. Hypoxia upregulated CD137 on murine endothelial cells. Treatment of tumor-bearing immunocompromised Rag(-/-) mice with agonist CD137 mAb did not elicit any measurable antiangiogenic effects. In contrast, agonist mAb stimulated tumor endothelial cells, increasing cell surface expression of the adhesion molecules intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin. When adoptively transferred into mice, activated T lymphocytes derived from CD137-deficient animals entered more avidly into tumor tissue after treatment with agonist mAb. This effect could be neutralized with anti-ICAM-1 and anti-VCAM-1 blocking antibodies. Thus, stimulation of CD137 not only enhanced T-cell activation but also augmented their trafficking into malignant tissue, through direct actions on the blood vessels that irrigate the tumor. Our findings identify an additional mechanism of action that can explain the immunotherapeutic effects of agonist CD137 antibodies.
Permanent link: http://hdl.handle.net/10171/20317
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista
DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista

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