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 -
Endika Prieto Fernandez
Juan de la Cierva Fellow -
Ana García del Rio
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Leire Egia Mendikute
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Samanta Romina Zanetti
TECHNICIANS / DOCTORAL CANDIDATES -
Asier Antoñana Vildosola
INPhINIT Fellow "La Caixa" -
Ane Granja Martinez
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Adrian Barreira Manrique
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Ander de Blas Martín
AECC Predoctoral Felow -
So Young Lee
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Alexandre Bosch Martínez
AECC Predoctoral Felow -
Luisa Pareja Arcos
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Borja Jimenez Lasheras
Members
Latest Publications
The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes
Mercado-Gomez, M;Prieto-Fernandez, E;Goikoetxea-Usandizaga, N;Vila-Vecilla, L;Azkargorta, M;Bravo, M;Serrano-Macia, M;Egia-Mendikute, L;Rodriguez-Agudo, R;Lachiondo-Ortega, S;Lee, SY;Gine, AE;Gil-Pitarch, ...
COMMUNICATIONS BIOLOGY
2022-08-17
Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients
Serrano-Macia, M;Lachiondo-Ortega, S;Iruzubieta, P;Goikoetxea-Usandizaga, N;Bosch, A;Egia-Mendikute, L;Jimenez-Lasheras, B;Azkargorta, M;Elortza, F;Martinez-Redondo, D;Castro, B;Lozano, JJ;Nogueiras, ...
CELL DEATH DISCOVERY
2022-07-12
Assessing the Mobility of Severe Acute Respiratory Syndrome Coronavirus-2 Spike Protein Glycans by Structural and Computational Methods
Stagnoli, S;Peccati, F;Connell, SR;Martinez-Castillo, A;Charro, D;Millet, O;Bruzzone, C;Palazon, A;Arda, A;Jimenez-Barbero, J;Ereno-Orbea, J;Abrescia, NGA;Jimenez-Oses, G
FRONTIERS IN MICROBIOLOGY
2022-04-15
Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment
Araujo, AM;Abaurrea, A;Azcoaga, P;Lopez-Velazco, JI;Manzano, S;Rodriguez, J;Rezola, R;Egia-Mendikute, L;Valdes-Mora, F;Flores, JM;Jenkins, L;Pulido, L;Osorio-Querejeta, I;Fernandez-Nogueira, ...
JOURNAL OF CLINICAL INVESTIGATION
2022-04-01
Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals
Egia-Mendikute, L;Bosch, A;Prieto-Fernandez, E;Lee, SY;Jimenez-Lasheras, B;del Rio, AG;Antonana-Vildosola, A;Bruzzone, C;Bizkarguenaga, M;Embade, N;Gil-Redondo, R;Martinez-Chantar, ML;Lopez-Hoyos, ...
COMMUNICATIONS BIOLOGY
2021-04-20
Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate
Prieto-Fernandez, E;Egia-Mendikute, L;Vila-Vecilla, L;Bosch, A;Barreira-Manrique, A;Lee, SY;Garcia-del Rio, A;Antonana-Vildosola, A;Jimenez-Lasheras, B;Moreno-Cugnon, L;Jimenez-Barbero, J;Berra, ...
EMERGING MICROBES & INFECTIONS
2021-01-01
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
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