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 POSTDOCTORAL RESEARCHER -
Ana García del Rio
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Samanta Romina Zanetti
TECHNICIANS / DOCTORAL CANDIDATES -
Leire Egia Mendikute
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So Young Lee
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Borja Jimenez Lasheras
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Asier Antoñana Vildosola
INPhINIT Fellow "La Caixa" -
Ander de Blas Martín
AECC Predoctoral Felow -
Luisa Pareja Arcos
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Paloma Velasco Beltrán
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Alexandre Bosch Martínez
AECC Predoctoral Felow -
Jone Etxaniz Díaz de Durana
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Ane Granja Martinez
Members
Latest Publications
Factor-inhibiting HIF (FIH) promotes lung cancer
García-del Río, AGD; Prieto-Fernández, E; Egia-Mendikute, L; Antonana-Vildosola, A; Jimenez-Lasheras, B; Lee, SY; Barreira-Manrique, A; Zanetti, SR; de Blas, A; Velasco-Beltrán, P; Bosch, A; ...
JCI INSIGHT
2023-10-23
Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death
Sauve, F; Nampoothiri, S; Clarke, SA; Fernandois, D; Coêlho, CFF; Dewisme, J; Mills, EG; Ternier, G; Cotellessa, L; Iglesias-Garcia, C; Mueller-Fielitz, H; Lebouvier, T; Perbet, R; Florent, ...
EBIOMEDICINE
2023-10-01
The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function
Foskolou, IP; Cunha, PP; Sanchez-Lopez, E; Minogue, EA; Nicolet, BP; Guislain, A; Jorgensen, C; Kostidis, S; Zandhuis, ND; Barbieri, L; Bargiela, D; Nathanael, D; Tyrakis, PA; Palazon, A; Giera, ...
CELL REPORTS
2023-09-26
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Lenza, MP; Egia-Mendikute, L; Antoñana-Vildosola, A; Soares, CO; Coelho, H; Corzana, F; Bosch, A; Manisha, P; Quintana, JI; Oyenarte, I; Unione, L; Moure, MJ; Azkargorta, M; Atxabal, U; Sobczak, ...
NATURE COMMUNICATIONS
2023-06-13
The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes
Mercado-Gómez, M; Prieto-Fernández, E; Goikoetxea-Usandizaga, N; Vila-Vecilla, L; Azkargorta, M; Bravo, M; Serrano-Maciá, M; Egia-Mendikute, L; Rodríguez-Agudo, R; Lachiondo-Ortega, S; Lee, ...
COMMUNICATIONS BIOLOGY
2022-08-17
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
INT CEL MOL BIO
Antoñana-Vildosola, A; Zanetti, SR; Palazon, A; Aranda, F; Berraondo, P; Galluzzi, L;
ADOPTIVE CELL TRANSFER
2022-01-01
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-Fernández, E; Egia-Mendikute, L; Vila-Vecilla, L; Bosch, A; Barreira-Manrique, A; Lee, SY; García-del Río, A; Antoñana-Vildosola, A; Jiménez-Lasheras, B; Moreno-Cugnon, L; Jiménez-Barbero, ...
EMERGING MICROBES & INFECTIONS
2021-01-01
Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment
Prieto-Fernandez, E; Egia-Mendikute, L; Bosch, A; del Río, AG; Jimenez-Lasheras, B; Antoñana-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