It is well recognised that the clinical response of immunotherapies depends on the ability of T-cells to mount an effective effector response, persist in treated patients and avoid exhaustion and toxicities. Several approaches to immunotherapy have shown promise in clinical trials, especially the use of immune checkpoint inhibitors and, more recently, autologous adoptive T-cell therapies. However, current state-of-the-art immunotherapies are only effective in a small fraction of patients, offering a medical need to be addressed in several cancer types.
Importantly, the tumor microenvironment has specific features that impact the immune response, including decreased oxygenation, aberrant vascularization and altered nutrient availability; all these influence the success of immunotherapies.
Our research is focused on elucidating the role of the oxygen sensing machinery in T cell function, and the link of hypoxia-driven metabolism and epigenetic modifications with T cell differentiation into effector and memory T cells within the context of cancer immunotherapy. Our current aims are to exploit these findings with a multi-disciplinary strategy, to deliver several early-stage drug discovery outputs. Our main objectives are:
1. Development of novel small molecule inhibitors to modulate the hypoxic response in T cells.
2. Therapeutic target discovery in T cells, focused on hypoxia-driven epigenetic modifications.
3. Development of hypoxia-responsive approaches for adoptive T cell therapy.
Successful completion of these aims will allow us to further innovate, harness this pathway for therapeutic potential and explore potential combinatorial approaches.
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Principal Investigator
Asís Palazón
ERC Starting Grant - Ramón y Cajal (RyC) Programme - Ikerbasque Research Associate POST DOCTORAL RESEARCHER -
Leire Egia Mendikute
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Ana García del Rio
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Laura Vila Vecilla
Juan de la Cierva Fellow -
TECHNICIANS / EARLY STAGE RESEARCHER
Endika Prieto Fernandez
Juan de la Cierva Fellow -
Alexandre Bosch Martínez
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Asier Antoñana Vildosola
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Ander de Blas Martín
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Adrián Barreira Manrique
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So Young Lee
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Miguel Tamayo
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Borja Jimenez Lasheras
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Ander Vidaurrazaga
Members
Latest Publications
SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum
Bruzzone, C;Bizkarguenaga, M;Gil-Redondo, R;Diercks, T;Arana, E;de Vicuna, AG;Seco, M;Bosch, A;Palazon, A;San Juan, I;Lain, A;Gil-Martinez, J;Bernardo-Seisdedos, G;Fernandez-Ramos, D;Lopitz-Otsoa, ...
ISCIENCE
2020-10-23
Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins
Lenza, MP;Oyenarte, I;Diercks, T;Quintana, JI;Gimeno, A;Coelho, H;Diniz, A;Peccati, F;Delgado, S;Bosch, A;Valle, M;Millet, O;Abrescia, NGA;Palazon, A;Marcelo, F;Jimenez-Oses, G;Jimenez-Barbero, ...
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2020-10-22
Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment
Prieto-Fernandez, E;Egia-Mendikute, L;Bosch, A;del Rio, AG;Jimenez-Lasheras, B;Antonana-Vildosola, A;Lee, SY;Palazon, A
FRONTIERS IN IMMUNOLOGY
2020-09-30
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
Rodriguez-Garcia, A;Palazon, A;Noguera-Ortega, E;Powell, DJ;Guedan, S
FRONTIERS IN IMMUNOLOGY
2020-06-17