Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism
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POSTER PRESENTATION
Open Access
Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism Sara Labiano1*, Asis Palazon1, Elixabet Bolaños-Mateo1, Arantza Azpilicueta1, Alfonso Rodriguez1, Aizea Morales-Kastresana1, Elena Marin1, Alfonso Gurpide2, Maria Rodriguez-Ruiz1, M Angela Aznar1, Maria Jure-Kunkel3, Ignacio Melero1 From Society for Immunotherapy of Cancer 29th Annual Meeting National Harbor, MD, USA. 6-9 November 2014
Hypoxia is a common feature in solid tumors that has been implicated in immune-evasion. Previous studies from our group have shown that hypoxia up-regulates the co-stimulatory receptor CD137 on activated T lymphocytes and on vascular endothelial cells. In this study, we show that exposure of mouse and human tumor cell lines to hypoxic conditions (1% O 2 ) promotes CD137 transcription. However, the resulting mRNA is predominantly an alternatively spliced form that encodes for a soluble variant, lacking the transmembrane domain. Accordingly, soluble CD137 (sCD137) is detectable by ELISA in the supernatant of hypoxia-exposed cell lines and in the serum of tumor-bearing mice. sCD137, as secreted by tumor cells, is able to bind to CD137-Ligand (CD137L). Our studies on primed T lymphocytes in coculture with stable transfectants for CD137L demonstrate that tumor-secreted sCD137 prevents co-stimulation of T lymphocytes. Such an effect results from preventing the interaction of CD137L with the transmembrane forms of CD137 expressed on T lymphocytes undergoing activation. This mechanism is interpreted as a molecular strategy deployed by tumors to repress lymphocyte co-stimulation via CD137/CD137L.
Published: 6 November 2014
doi:10.1186/2051-1426-2-S3-P218 Cite this article as: Labiano et al.: Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism. Journal for ImmunoTherapy of Cancer 2014 2(Suppl 3):P218.
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Authors’ details 1 Immunology and Immunotherapy, Center for Applied Medical Research, Pamplona, Spain. 2Oncology, CUN, Pamplona, Spain. 3Oncology Drug Discovery division, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA.
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1 Immunology and Immunotherapy, Center for Applied Medical Research, Pamplona, Spain Full list of author information is available at the end of the article
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© 2014 Labiano et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Cr
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