Mr. Hugo Arasanz Esteban
Oncoimmunology Group, Navarrabiomed, 31008 Pamplona, Spain
'%3e%3cpath%20d='M22.1642%2019.0924C21.7317%2018.068%2021.1041%2017.1375%2020.3163%2016.3527C19.5309%2015.5656%2018.6006%2014.9381%2017.5766%2014.5048C17.5674%2014.5002%2017.5582%2014.4979%2017.5491%2014.4933C18.9774%2013.4616%2019.9059%2011.7811%2019.9059%209.88504C19.9059%206.74408%2017.3611%204.19922%2014.2201%204.19922C11.0792%204.19922%208.53429%206.74408%208.53429%209.88504C8.53429%2011.7811%209.46282%2013.4616%2010.8912%2014.4956C10.882%2014.5002%2010.8728%2014.5025%2010.8636%2014.5071C9.83652%2014.9404%208.91487%2015.5617%208.1239%2016.355C7.33685%2017.1404%206.70933%2018.0707%206.276%2019.0947C5.85031%2020.0972%205.62072%2021.172%205.59967%2022.2609C5.59905%2022.2853%205.60335%2022.3097%205.61229%2022.3325C5.62123%2022.3553%205.63465%2022.376%205.65174%2022.3935C5.66883%2022.4111%205.68926%2022.425%205.71182%2022.4345C5.73437%2022.444%205.7586%2022.4489%205.78308%2022.4489H7.15868C7.25956%2022.4489%207.3398%2022.3686%207.3421%2022.2701C7.38795%2020.5001%208.09868%2018.8425%209.35506%2017.5861C10.655%2016.2862%2012.3814%2015.5709%2014.2201%2015.5709C16.0588%2015.5709%2017.7852%2016.2862%2019.0852%2017.5861C20.3415%2018.8425%2021.0523%2020.5001%2021.0981%2022.2701C21.1004%2022.3709%2021.1807%2022.4489%2021.2815%2022.4489H22.6571C22.6816%2022.4489%2022.7058%2022.444%2022.7284%2022.4345C22.751%2022.425%2022.7714%2022.4111%2022.7885%2022.3935C22.8056%2022.376%2022.819%2022.3553%2022.8279%2022.3325C22.8369%2022.3097%2022.8412%2022.2853%2022.8406%2022.2609C22.8176%2021.165%2022.5907%2020.0989%2022.1642%2019.0924ZM14.2201%2013.8284C13.1678%2013.8284%2012.1773%2013.418%2011.4322%2012.6729C10.6871%2011.9278%2010.2767%2010.9374%2010.2767%209.88504C10.2767%208.83271%2010.6871%207.84227%2011.4322%207.09715C12.1773%206.35204%2013.1678%205.94165%2014.2201%205.94165C15.2724%205.94165%2016.2629%206.35204%2017.008%207.09715C17.7531%207.84227%2018.1635%208.83271%2018.1635%209.88504C18.1635%2010.9374%2017.7531%2011.9278%2017.008%2012.6729C16.2629%2013.418%2015.2724%2013.8284%2014.2201%2013.8284Z'%20fill='%238590A2'/%3e%3c/g%3e%3c/svg%3e)
Co-authors
Following
Followers
Research Focus & Metrics
Explore full metrics on Scilit
Academic Career Length
12Years (2015-Present)
(Calculated once Scilit publication data is synced: current year − year of first publication + 1)
Representative Publications
View All Publications1 August 2017 in Cell Reports
Journal Article
MGMaria Gato-Cañas
Maria Gato-Cañas
MZMiren Zuazo
Miren Zuazo
Hugo Arasanz EstebanMIMaria Ibañez-Vea
Maria Ibañez-Vea
LLLaura Lorenzo
Laura Lorenzo
DEDavid Escors
David Escors +11
PDL1 blockade produces remarkable clinical responses, thought to occur by T cell reactivation through prevention of PDL1-PD1 T cell inhibitory interactions. Here, we find that PDL1 cell-intrinsic signaling protects cancer cells from interferon (IFN) cytotoxicity and accelerates tumor progression. PDL1 inhibited IFN signal transduction through a conserved class of sequence motifs that mediate crosstalk with IFN signaling. Abrogation of PDL1 expression or antibody-mediated PDL1 blockade strongly sensitized cancer cells to IFN cytotoxicity through a STAT3/caspase-7-dependent pathway. Moreover, somatic mutations found in human carcinomas within these PDL1 sequence motifs disrupted motif regulation, resulting in PDL1 molecules with enhanced protective activities from type I and type II IFN cytotoxicity. Overall, our results reveal a mode of action of PDL1 in cancer cells as a first line of defense against IFN cytotoxicity.
28 September 2018 in Signal Transduction and Targeted Therapy
Journal Article
DEDavid Escors
David EscorsMGMaría Gato-Cañas
María Gato-Cañas
MZMiren Zuazo
Miren Zuazo
Hugo Arasanz EstebanMGMaría Jesus García-Granda
María Jesus García-Granda
GKGrazyna Kochan
Grazyna Kochan +1
Programmed cell death-1 ligand-1 (PD-L1) overexpression in cancer cells accelerates tumor progression. PD-L1 possesses two main pro-oncogenic functions. First, PD-L1 is a strong immunosuppressive molecule that inactivates tumor-specific T cells by binding to the inhibitory receptor PD-1. Second, PD-L1 function relies on the delivery of intrinsic intracellular signals that enhance cancer cell survival, regulate stress responses and confer resistance toward pro-apoptotic stimuli, such as interferons. Here, we review the current knowledge on intracellular signal transduction pathways regulated by PD-L1, describe its associated signalosome and discuss potential combinations of targeted therapies against the signalosome with PD-L1/PD-1 blockade therapies.
19 April 2017 in Oncotarget
Journal Article
Hugo Arasanz EstebanMGMaria Gato-Cañas
Maria Gato-Cañas
MZMiren Zuazo
Miren Zuazo
MIMaria Ibañez-Vea
Maria Ibañez-Vea
KBKarine Breckpot
Karine BreckpotDEDavid Escors
David Escors +1
PD1 signal transduction pathways in T cells
Journal Article
LCLuisa Chocarro
Luisa ChocarroEBEster Blanco
Ester BlancoMZMiren Zuazo
Miren ZuazoHugo Arasanz EstebanAGAna Isabel Bocanegra Gondan
Ana Isabel Bocanegra GondanDEDavid Escors
David Escors +8
Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies, and it is considered a potential next-generation cancer immunotherapy target in human therapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 and its relationship with other immune checkpoint molecules remain poorly understood. This is partly caused by the presence of non-conventional signaling motifs in its intracellular domain that are different from other conventional immunoregulatory signaling motifs but with similar inhibitory activities. Here we summarize the current understanding of LAG-3 signaling and its role in LAG-3 functions, from its mechanisms of action to clinical applications.
6 June 2019 in EMBO Molecular Medicine
Journal Article
MZMiren Zuazo
Miren Zuazo
Hugo Arasanz EstebanGFGonzalo Fernández‐Hinojal
Gonzalo Fernández‐Hinojal
MGMaria Jesus García‐Granda
Maria Jesus García‐Granda
MGMaría Gato
María Gato
DEDavid Escors
David Escors +9
The majority of lung cancer patients progressing from conventional therapies are refractory to PD‐L1/PD‐1 blockade monotherapy. Here, we show that baseline systemic CD4 immunity is a differential factor for clinical responses. Patients with functional systemic CD4 T cells included all objective responders and could be identified before the start of therapy by having a high proportion of memory CD4 T cells. In these patients, CD4 T cells possessed significant proliferative capacities, low co‐expression of PD‐1/LAG‐3 and were responsive to PD‐1 blockade ex vivo and in vivo . In contrast, patients with dysfunctional systemic CD4 immunity did not respond even though they had lung cancer‐specific T cells. Although proficient in cytokine production, CD4 T cells in these patients proliferated very poorly, strongly co‐upregulated PD‐1/LAG‐3, and were largely refractory to PD‐1 monoblockade. CD8 immunity only recovered in patients with functional CD4 immunity. T‐cell proliferative dysfunctionality could be reverted by PD‐1/LAG‐3 co‐blockade. Patients with functional CD4 immunity and PD‐L1 tumor positivity exhibited response rates of 70%, highlighting the contribution of CD4 immunity for efficacious PD‐L1/PD‐1 blockade therapy.
7 April 2020 in Frontiers in Pharmacology
Journal Article
LCLuisa Chocarro
Luisa ChocarroMZMiren Zuazo
Miren Zuazo
Hugo Arasanz EstebanABAna Bocanegra
Ana Bocanegra
CHCARLOS HERNANDEZ
CARLOS HERNANDEZDEDavid Escors
David Escors +5
Cancer immunotherapies targeting immune checkpoints such as programmed cell-death protein 1 (PD-1) and its ligand programmed cell-death 1 ligand 1 (PD-L1), are revolutionizing cancer treatment and transforming the practice of medical oncology. However, despite all the recent successes of this type of immunotherapies, most patients are still refractory and present either intrinsic resistance or acquired resistance. Either way, this is a major clinical problem and one of the most significant challenges in oncology. Therefore, the identification of biomarkers to predict clinical responses or for patient stratification by probability of response has become a clinical necessity. However, the mechanisms leading to PD-L1/PD-1 blockade resistance are still poorly understood. A deeper understanding of the basic mechanisms underlying resistance to cancer immunotherapies will provide insight for further development of novel strategies designed to overcome resistance and treatment failure. Here we discuss some of the major molecular mechanisms of resistance to PD-L1/PD-1 immune checkpoint blockade and argue whether tumor intrinsic or extrinsic factors constitute main determinants of response and resistance.
About Me
I am currently a specialist physician in Medical Oncology at Hospital Universitario de Navarra and postdoctoral researcher of the Oncoimmunology Group at Navarrabiomed (Spain). In 2015 I began my own PhD project focused in molecular pathways of resistance and escape to treatment in pancreatic adenocarcinoma. The defense of the whole investigation was succesfully performed in February 2020, and it was awarded with the calification "Excellent Cum Laude". I am also involved since 2017 in a traslational research of immunotherapy in non-small cell lung cancer, in which we have identified a predictive biomarker of response to immune checkpoint inhibitors, along with a tool for early identification of hyperprogressive disease. This investigation led to a publication in a D1 journal, another article in a Q1 one, along with several communications in international congresses.
Lastly, in 2019 I was awarded with the "Clínico Junior" grant by Asociación Española Contra el Cáncer (AECC). The translational funded project explores the mechanistics of response to immunotherapy and chemoimmunotherapy in untreated non-small cell lung cancer. It is currently ongoing, and preliminary results have been already presented at different scientific meetings.