Comunicaciones a congresos, conferencias (CIMA)
Permanent URI for this collectionhttps://hdl.handle.net/10171/70260
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7 results
Results
- Id1 and PD-1 Combined Blockade Impairs Tumor Growth and Survival of KRAS-mutant Lung Cancer by Stimulating PD-L1 Expression and Tumor Infiltrating CD8+ T Cells(2020) Gil-Bazo, I. (Ignacio); Pio, R. (Rubén); Román, M. (Marta); Puyalto, A. (Ander); Collantes, M. (María); Lozano-Moreda, T. (Teresa); Vicent, S. (Silvestre); Garcia-Ros, D. (David); Villalba-Esparza, M. (María); Caglevic, C. (Christian); Ecay, M. (Margarita); Rodríguez-Remírez, M. (M.); Alignani, D. (Diego); Rolfo, C. (Christian); Guruceaga, E. (Elizabeth); Moreno, H. (Haritz); Andrea, C.E. (Carlos Eduardo) de; Ortiz-Espinosa, S. (Sergio); Vilalta, A. (Anna); Torregrosa, M.S. (María Soledad); Baraibar-Argota, I. (Iosune); Lopez, I. (Inés); Calvo-González, A. (Alfonso); Ajona, D. (Daniel); Oliver, A. (Ana); Lasarte, J.J. (Juan José)The use of PD-1/PD-L1 checkpoint inhibitors in advanced NSCLC is associated with longer survival. However, many patients do not benefit from PD-1/PD-L1 blockade, largely because of immunosuppression. New immunotherapy-based combinations are under investigation in an attempt to improve outcomes. Id1 (inhibitor of differentiation 1) is involved in immunosuppression. In this study, we explored the potential synergistic effect of the combination of Id1 inhibition and pharmacological PD-L1 blockade in three different syngeneic murine KRAS-mutant lung adenocarcinoma models. TCGA analysis demonstrated a negative and statistically significant correlation between PD-L1 and Id1 expression levels. This observation was confirmed in vitro in human and murine KRAS-driven lung cancer cell lines. In vivo experiments in KRAS-mutant syngeneic and metastatic murine lung adenocarcinoma models showed that the combined blockade targeting Id1 and PD-1 was more effective than each treatment alone in terms of tumor growth impairment and overall survival improvement. Mechanistically, multiplex quantification of CD3+/CD4+/CD8+ T cells and flow cytometry analysis showed that combined therapy favors tumor infiltration by CD8+ T cells, whilst in vivo CD8+ T cell depletion led to tumor growth restoration. Co-culture assays using CD8+ cells and tumor cells showed that T cells present a higher antitumor effect when tumor cells lack Id1 expression. These findings highlight that Id1 blockade may contribute to a significant immune enhancement of antitumor efficacy of PD-1 inhibitors by increasing PD-L1 expression and harnessing tumor infiltration of CD8+ T lymphocytes.
- Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011(BioMed Central, 2012) Gajewski, T.F. (Thomas F.); Martinez-Forero, I. (Iván); Melero, I. (Ignacio); Topalian, S.L. (Suzanne L.); Korman, A.J. (Alan J.); Okada, H. (Hideho)Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and “perceived” business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace.
- Proceedings of the workshop "Neuroanatomical Tracing and Systems Neuroscience: the State of the Art", 7th FENS meeting, Amsterdam, The Netherlands, July 3, 2010(Elsevier, 2010) Wouterlood, F.G. (Floris G.); Lanciego, J.L. (José Luis)
- Proceedings of the 2007 international brain research organisation satellite meeting "movement disorders: focus on the thalamus and basal ganglia" held in Sydney, Australia, 10-11 July 2007(Elsevier, 2009) Smith, Y. (Yoland); Lanciego, J.L. (José Luis); Kassiou, M. (M.); Gundlach, A.L. (A. L.); Henderson, J.M. (J. M.); International Brain Research Satellite Meeting. Organising and Editorial Committee
- Decreased glucose-derivate uptake in primary somatosensorial cortex in the brain of female AIP mice. | International Porphyrins and Porphyria Meeting (10-13 April 2011. Cardiff, Wales, UK)(2011-04-13) Pozo, M.A. (Miguel Ángel); Delgado, M. (Mercedes); Benito, M. (Marina); Collantes, M. (María); Lanciego, J.L. (José Luis); Peñuelas-Sanchez, I. (Ivan); Desco, M. (Manuel); Prieto-Azcárate, E. (Elena); Molinet-Dronda, F. (Francisco); Unzu, C. (Carmen); Prieto, J. (Jesús); Enriquez-de-Salamanca, R. (Rafael); Fontanellas-Romá, A. (Antonio); Garcia-Garcia, L. (Luis); Rodriguez, I. (Ignacio)
- Construction of different radionuclide templates of rat brains and their use on a new statistic parametric mapping analysis protocol for PET studies. | International WorkshopCNA´10: Bio-medical applications of Micro-PET (20-21 September 2010. Sevilla, Spain)(2010-09-20) Pozo, M.A. (Miguel Ángel); Delgado, M. (Mercedes); Juri, C. (Carlos); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Prieto-Azcárate, E. (Elena); Molinet-Dronda, F. (Francisco); Fernandez, M.E. (M. E.); Garcia-Garcia, L. (Luis)This work shows the development of protocols to create new 18F‐FDG and 11C‐DTBZ (dyhidrotetrabenazine, a VMAT2 transporter ligand) templates of rat brain for spatial normalisation and definition of standardised areas in images used for setting up SPM analysis of PET data.
- Automated Quantitative Analysis of a Mouse Model of Chronic Pulmonary Inflammation using Micro X-ray Computed Tomography(2011-05-02) Ortiz-de-Solorzano, C. (Carlos); Reinhardt, J.M. (Joseph M.); Artaechevarria-Artieda, X. (Xabier); Muñoz-Barrutia, A. (Arrate); Perez-Martin, D. (Daniel)Micro-CT has emerged as an excellent tool for in-vivo imaging of the lungs of small laboratory animals. Several studies have shown that it can be used to assess the evolution of pulmonary lung diseases in longitudinal studies. However, most of them rely on non-automatic tools for image analysis, or are merely qualitative. In this article, we present a longitudinal, quantitative study of a mouse model of silica-induced pulmonary inflammation. To automatically assess disease progression, we have devised and validated a lung segmentation method that combines threshold-based segmentation, atlas-based segmentation and level sets. Our volume measurements, based on the automatic segmentations, point at a compensation mechanism which leads to an increase of the healthy lung volume in response to the loss of functional tissue caused by inflammation.