Publicaciones científicas

Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism

Labiano S (1), Palazón A (1), Bolaños E (1), Azpilikueta A (1), Sánchez-Paulete AR (1), Morales-Kastresana A (1), Quetglas JI (1), Perez-Gracia JL (1), Gúrpide A (1), Rodriguez-Ruiz M (1), Aznar MA (1), Jure-Kunkel M (2), Berraondo P (1), Melero I (1).
(1) CIMA, Clínica Universidad de Navarra, University of Navarra and IDISNA , Pamplona, Spain.
(2) Bristol-Myers Squibb Pharmaceutical Research Institute , Princeton, NJ, USA.

Revista: Oncoimmunology

Fecha: 06-dic-0029

Inmunología e Inmunoterapia Oncología Médica


Hypoxia is a common feature in solid tumors that has been implicated in immune evasion. Previous studies from our group have shown that hypoxia upregulates 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% O2) 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 co-culture 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.

Indeed, silencing CD137 with shRNA renders more immunogenic tumor-cell variants upon inoculation to immunocompetent mice but which readily grafted on immunodeficient or CD8+ T-cell-depleted mice. These mechanisms are interpreted as a molecular strategy deployed by tumors to repress lymphocyte co-stimulation via CD137/CD137L.

CITA DEL ARTÍCULO  Oncoimmunology. 2015 Jun 24;5(1):e1062967



La Clínica es el hospital privado con mayor dotación tecnológica de España, todo en un único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra


Los profesionales de la Clínica realizan una labor continuada de investigación y formación, siempre en beneficio del paciente.

Imagen profesionales de la Clínica Universidad de Navarra


Conozca por qué somos diferentes a otros centros sanitarios. Calidad, rapidez, comodidad y resultados.

Imagen del edificio de la Clínica Universidad de Navarra