ERC Starting Grant Ramón y Cajal (RyC) Programme Ikerbasque Research Associate
Asís Palazón is a pharmacist (2006) and biochemist (2008), degrees obtained at the University of Navarre.
He defended his PhD thesis in Cancer Immunology and Immunotherapy in 2012 at CIMA (Pamplona, Spain), supervised by Prof. Ignacio Melero. During this early career stage, he contributed to the understanding of the mechanism of action of anti-CD137 agonist therapeutic antibodies, combinatorial approaches, and the influence of tumor oxygenation in the efficacy of immunotherapies. His work led to first-authored publications in Cancer Research, Clinical Cancer Research, and Cancer Discovery; and several international collaborations.
In 2012, he joined Prof. Randall Johnson's lab at the University of Cambridge for a postdoctoral stay supported by a Marie Curie Intra-European fellowship, with the aim of studying the role of hypoxia on immune responses in cancer. His work was published in high profile journals, including Cancer Cell, Cell Metabolism, Immunity and Nature. In 2017, he joined the pharmaceutical industry (Medimmune, Cambridge, UK), contributing to a range of preclinical activities from target identification to IND-application in the field of immuno-oncology.
In early 2019, Asís joined CICbiogune as a Principal Investigator where he leads the Cancer Immunology and Immunotherapy lab supported by an ERC Starting grant (2018). The lab has a core focus on immuno-oncology, specifically on target discovery and drug development, to exploit several opportunities that the hypoxia pathway in T cells offers for the treatment of cancer.
Latest Publications
2023
2022
2021
2020
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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Lorena Pérez Gutiérrez
Juan de la Cierva Fellow TECHNICIANS / DOCTORAL CANDIDATES -
Jone Etxaniz Díaz de Durana
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Borja Jimenez Lasheras
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Alexandre Bosch Martínez
AECC Predoctoral Felow -
Eunate Valdaliso Díez
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Asier Antoñana Vildosola
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So Young Lee
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Paloma Velasco Beltrán
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Ander de Blas Martín
AECC Predoctoral Felow
Members
POSTDOCTORAL RESEARCHERLatest Publications
SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer.
Lachiondo-Ortega, Sofia; Rejano-Gordillo, Claudia M; Simon, Jorge; Lopitz-Otsoa, Fernando; C Delgado, Teresa; Mazan-Mamczarz, Krystyna; Goikoetxea-Usandizaga, Naroa; Zapata-Pavas, L Estefania; ...
Cell reports
2024-03-26
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
Enabling CAR-T cells for solid tumors: Rage against the suppressive tumor microenvironment
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