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1. TGFBI expression is associated with a better response to chemotherapy in NSCLC

Author

Pío Ruben, Lozano María D, Salvo Elisabeth, Ponz-Sarvisé Mariano, Agorreta Jackeline, Pajares María J, Irigoyen Marta, Gil-Bazo Ignacio, and Rouzaut Ana

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Lung cancer is one of the most prevalent neoplasias in developed countries. Advances in patient survival have been limited and the identification of prognostic molecules is needed. Resistance to treatment is strongly related to tumor cell adhesion to the extracellular matrix and alterations in the quantity and nature of molecules constituting the tumor cell niche. Recently, transforming growth factor beta-induced protein (TGFBI), an extracellular matrix adaptor protein, has been reported to be differentially expressed in transformed tissues. Loss of TGFBI expression has been described in several cancers including lung carcinoma, and it has been suggested to act as a tumor suppressor gene. Results To address the importance of TGFBI expression in cancer progression, we determined its expression in NSCLC clinical samples using immunohistochemistry. We identified a strong association between elevated TGFBI expression and the response to chemotherapy. Furthermore, we transiently over-expressed and silenced TGFBI in human NSCLC cell lines. Cells over-expressing TGFBI displayed increased sensitivity to etoposide, paclitaxel, cisplatin and gemcitabine. We observed that TGFBI-mediated induction of apoptosis occurred through its binding to αvβ3 integrin. We also determined that full-length TGFBI did not induce caspase 3/7 activation but its proteolytic fragments that were < 3 kDa in size, were able to activate caspase 3, 7 and 8. This pro-apoptotic effect was blocked by anti-αvβ3 integrin antibodies. Conclusions The results shown here indicate that TGFBI is a predictive factor of the response to chemotherapy, and suggest the use of TGFBI-derived peptides as possible therapeutic adjuvants for the enhancement of responses to chemotherapy.

Published
2010
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4. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity

Author

Teijeira, Álvaro, Garasa, Saray, Gato, María, Alfaro, Carlos, Migueliz, Itziar, Cirella, Assunta, de Andrea, Carlos, Ochoa, Maria Carmen, Otano, Itziar, Etxeberria, Iñaki, Andueza, Maria Pilar, Nieto, Celia P., Resano, Leyre, Azpilikueta, Arantza, Allegretti, Marcello, de Pizzol, Maria, Ponz-Sarvisé, Mariano, Rouzaut, Ana, Sanmamed, Miguel F., Schalper, Kurt, Carleton, Michael, Mellado, Mario, Rodriguez-Ruiz, María E., Berraondo, Pedro, Perez-Gracia, Jose L., and Melero, Ignacio

Published
2020
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9. CRMP2 as a Candidate Target to Interfere with Lung Cancer Cell Migration

Author

Xabier Morales, Rafael Peláez, Saray Garasa, Carlos Ortiz de Solórzano, and Ana Rouzaut

Subjects
CRMP2, lung cancer, migration, cytoskeleton, Microbiology, QR1-502
Abstract

Collapsin response mediator protein 2 (CRMP2) is an adaptor protein that adds tubulin dimers to the growing tip of a microtubule. First described in neurons, it is now considered a ubiquitous protein that intervenes in processes such as cytoskeletal remodeling, synaptic connection and trafficking of voltage channels. Mounting evidence supports that CRMP2 plays an essential role in neuropathology and, more recently, in cancer. We have previously described a positive correlation between nuclear phosphorylation of CRMP2 and poor prognosis in lung adenocarcinoma patients. In this work, we studied whether this cytoskeleton molding protein is involved in cancer cell migration. To this aim, we evaluated CRMP2 phosphorylation and localization in the extending lamella of lung adenocarcinoma migrating cells using in vitro assays and in vivo confocal microscopy. We demonstrated that constitutive phosphorylation of CRMP2 impaired lamella formation, cell adhesion and oriented migration. In search of a mechanistic explanation of this phenomenon, we discovered that CRMP2 Ser522 phospho-mimetic mutants display unstable tubulin polymers, unable to bind EB1 plus-Tip protein and the cortical actin adaptor IQGAP1. In addition, integrin recycling is defective and invasive structures are less evident in these mutants. Significantly, mouse xenograft tumors of NSCLC expressing CRMP2 phosphorylation mimetic mutants grew significantly less than wild-type tumors. Given the recent development of small molecule inhibitors of CRMP2 phosphorylation to treat neurodegenerative diseases, our results open the door for their use in cancer treatment.

Published
2021
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11. Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

Author

Alvaro Teijeira, Saray Garasa, Carlos Luri-Rey, Carlos de Andrea, Maria Gato, Carmen Molina, Tsuneyasu Kaisho, Assunta Cirella, Arantza Azpilikueta, Steffanie K. Wculek, Josune Egea, Irene Olivera, Inmaculada Rodriguez, Ana Rouzaut, Vladislav Verkhusha, Karmele Valencia, David Sancho, Pedro Berraondo, Ignacio Melero, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia (España), Agencia Estatal de Investigación (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Unión Europea. Comisión Europea. H2020, Comunidad Foral de Navarra (España), Mark Foundation, Fundación BBVA, and Fundación Olga Torres

Subjects
Mice, Cancer Research, Oncology, Liver Neoplasms, Animals, Antibodies, Monoclonal, Diphtheria Toxin, Mice, Transgenic, Dendritic Cells, Immunotherapy, CD8-Positive T-Lymphocytes
Abstract

The ability of conventional type-1 dendritic cells (cDC1) to cross-present tumor antigens to CD8+ T cells is critical for the induction of antitumor cytotoxic T lymphocytes. Mice that are constitutively deficient in cDC1 cells have been reported to fail to respond to immunotherapy strategies based on checkpoint inhibitors. However, further work is needed to clarify the precise time during immunotherapy treatment that cDC1 cells are required for the beneficial effect of treatment. Here, we used a refined XCR1-DTR-Venus transgenic mouse model to acutely deplete cDC1 cells and trace their behavior using intravital microscopy. Diphtheria toxin-mediated cDC1 depletion prior to immunotherapy treatment with anti-PD-1 and/or anti-CD137 immunostimulatory monoclonal antibodies (mAbs) completely ablated anti-tumor efficacy. The efficacy of adoptive T-cell therapy was also hampered by prior cDC1 depletion. After the onset of immunotherapy treatment, depletion of cDC1s only moderately reduced the therapeutic efficacy of anti-PD-1 and anti-CD137 mAbs. Intravital microscopy of liver-engrafted tumors revealed changes in the intratumoral behavior of cDC1 cells in mice receiving immunotherapy, and treatment with diphtheria toxin to deplete cDC1s impaired tumor T-cell infiltration and function. These results reveal that the functional integrity of the cDC1 compartment is required at the onset of various immunotherapies to successfully treat established tumors. This work was supported by Spanish Ministry of Economy and Competitiveness and Spanish Ministry of Research (MINECO SAF2014-52361-R and SAF 2017-83267-C2-1R and PID2020-112892RB-100, PID2020-113174-RA-100 [AEI/FEDER,UE], financed by MCIN/AEI/10.13039/501100011033), Cancer Research Institute under the CRI-CLIP, Asociación Española Contra el Cancer (AECC) Foundation under Grant GCB15152947MELE, Joint Translational Call for Proposals 2015 (JTC 2015) TRANSCAN-2 (code: TRS-2016-00000371), projects PI14/01686, PI13/00207, PI16/00668, PI19/01128, funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF, “A way to make Europe”), European Commission within the Horizon 2020 Programme (PROCROP - 635122), Gobierno de Navarra Proyecto LINTERNA Ref: 0011–1411, Mark Foundation, Fundación BBVA and Fundación Olga Torres. AT is supported by the Ramon y Cajal program from the Spanish Ministry of Science (RYC2019-026406-I financiada por MCIN/AEI /10.13039/501100011033 y por El FSE invierte en tu futuro). Sí

Published
2022
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13. Data from Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation

Author

Teijeira, Alvaro, primary, Labiano, Sara, primary, Garasa, Saray, primary, Etxeberria, Iñaki, primary, Santamaría, Eva, primary, Rouzaut, Ana, primary, Enamorado, Michel, primary, Azpilikueta, Arantza, primary, Inoges, Susana, primary, Bolaños, Elixabet, primary, Aznar, Maria Angela, primary, Sánchez-Paulete, Alfonso R., primary, Sancho, David, primary, and Melero, Ignacio, primary

Published
2023
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14. Supplemental Figures 1-10 from Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation

Author

Teijeira, Alvaro, primary, Labiano, Sara, primary, Garasa, Saray, primary, Etxeberria, Iñaki, primary, Santamaría, Eva, primary, Rouzaut, Ana, primary, Enamorado, Michel, primary, Azpilikueta, Arantza, primary, Inoges, Susana, primary, Bolaños, Elixabet, primary, Aznar, Maria Angela, primary, Sánchez-Paulete, Alfonso R., primary, Sancho, David, primary, and Melero, Ignacio, primary

Published
2023
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16. Data from Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation

Author

Ignacio Melero, David Sancho, Alfonso R. Sánchez-Paulete, Maria Angela Aznar, Elixabet Bolaños, Susana Inoges, Arantza Azpilikueta, Michel Enamorado, Ana Rouzaut, Eva Santamaría, Iñaki Etxeberria, Saray Garasa, Sara Labiano, and Alvaro Teijeira

Abstract

T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression. Mass and function of mitochondria in tumor-reactive CD8+ T cells from cancer-bearing mice were invigorated by agonist mAb to CD137, whereas mitochondrial baseline mass and function were depressed in CD137-deficient tumor reactive T cells. Tumor rejection induced by the synergistic combination of adoptive T-cell therapy and agonistic anti-CD137 was critically dependent on OPA-1 expression in transferred CD8+ T cells. Moreover, stimulation of CD137 with CD137 mAb in short-term cultures of human tumor-infiltrating lymphocytes led to mitochondria enlargement and increased transmembrane potential. Collectively, these data point to a critical link between mitochondrial morphology and function and enhanced antitumor effector activity upon CD137 costimulation of T cells. Cancer Immunol Res; 6(7); 798–811. ©2018 AACR.

Published
2023
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17. Supplemental Figures 1-10 from Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation

Author

Ignacio Melero, David Sancho, Alfonso R. Sánchez-Paulete, Maria Angela Aznar, Elixabet Bolaños, Susana Inoges, Arantza Azpilikueta, Michel Enamorado, Ana Rouzaut, Eva Santamaría, Iñaki Etxeberria, Saray Garasa, Sara Labiano, and Alvaro Teijeira

Abstract

Figure S1 shows that CD8 T cells with high mitochondrial transmembrane potential after CD137 stimulation have enlarged mitochondria. Fig S2 shows that CD137 induced mitochondrial changes are not due to enrichment of specific CD8 T cells subsets. Figure S3 shows that mitochondrial enhanced functions induced by CD137 activation are not a consequence of autocrine secretion of cytokines. Fig S4 shows that spare respiratory capacity induced by CD137 activation is dependent on fatty acid oxidation. Figure S5 explores regulation of mitochondrial biogenesis and fusion related genes upon CD137 activation. Fig S6 shows functional effects of OPA knockdown in CD8 T cells. Figure S7 shows the implication of Akt pathway on enhanced mitochondrial function by CD137 activation. Figure S8 shows that CD137KO CD8 T cells have intrinsic mitochondrial defects upon CD28 activation. Figure S9 shows that CD137 activation enhances mitochondrial parameters in tumor infiltrating lymphocytes. Fig S10 shows engrafment abilities and memory markers of OTI cells in B16OVA tumor bearing mice upon OPA silencing and CD137 mAb treatment.

Published
2023
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18. Supplementary video 3 from Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

Author

Teijeira, Alvaro, primary, Garasa, Saray, primary, Luri-Rey, Carlos, primary, de Andrea, Carlos, primary, Gato, Maria, primary, Molina, Carmen, primary, Kaisho, Tsuneyasu, primary, Cirella, Assunta, primary, Azpilikueta, Arantza, primary, Wculek, Steffanie K., primary, Egea, Josune, primary, Olivera, Irene, primary, Rodriguez, Inmaculada, primary, Rouzaut, Ana, primary, Verkhusha, Vladislav, primary, Valencia, Karmele, primary, Sancho, David, primary, Berraondo, Pedro, primary, and Melero, Ignacio, primary

Published
2023
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19. Supplementary methods and supplementary figure legends from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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20. Supplementary figure 3 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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21. Supplementary figure 2 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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22. Supplementary Figure Legend from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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23. Supplementary video 1 from Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

Author

Teijeira, Alvaro, primary, Garasa, Saray, primary, Luri-Rey, Carlos, primary, de Andrea, Carlos, primary, Gato, Maria, primary, Molina, Carmen, primary, Kaisho, Tsuneyasu, primary, Cirella, Assunta, primary, Azpilikueta, Arantza, primary, Wculek, Steffanie K., primary, Egea, Josune, primary, Olivera, Irene, primary, Rodriguez, Inmaculada, primary, Rouzaut, Ana, primary, Verkhusha, Vladislav, primary, Valencia, Karmele, primary, Sancho, David, primary, Berraondo, Pedro, primary, and Melero, Ignacio, primary

Published
2023
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24. Data from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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25. Supplementary table 1 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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26. Supplementary figure 6 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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27. Supplementary figures and methods from Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

Author

Teijeira, Alvaro, primary, Garasa, Saray, primary, Luri-Rey, Carlos, primary, de Andrea, Carlos, primary, Gato, Maria, primary, Molina, Carmen, primary, Kaisho, Tsuneyasu, primary, Cirella, Assunta, primary, Azpilikueta, Arantza, primary, Wculek, Steffanie K., primary, Egea, Josune, primary, Olivera, Irene, primary, Rodriguez, Inmaculada, primary, Rouzaut, Ana, primary, Verkhusha, Vladislav, primary, Valencia, Karmele, primary, Sancho, David, primary, Berraondo, Pedro, primary, and Melero, Ignacio, primary

Published
2023
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28. Supplementary Figure 2 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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29. Supplementary Figure 4 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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30. Supplementary Figure 1 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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31. Supplementary Figure 7 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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32. Supplementary figure 4 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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33. Supplementary Methods from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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34. Supplementary figure 5 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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35. Supplementary video 2 from Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

Author

Teijeira, Alvaro, primary, Garasa, Saray, primary, Luri-Rey, Carlos, primary, de Andrea, Carlos, primary, Gato, Maria, primary, Molina, Carmen, primary, Kaisho, Tsuneyasu, primary, Cirella, Assunta, primary, Azpilikueta, Arantza, primary, Wculek, Steffanie K., primary, Egea, Josune, primary, Olivera, Irene, primary, Rodriguez, Inmaculada, primary, Rouzaut, Ana, primary, Verkhusha, Vladislav, primary, Valencia, Karmele, primary, Sancho, David, primary, Berraondo, Pedro, primary, and Melero, Ignacio, primary

Published
2023
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36. Supplementary Figure 5 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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37. Supplementary Figure 3 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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38. Supplementary figure 1 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Rodriguez-Ruiz, María E., primary, Rodriguez, Inmaculada, primary, Garasa, Saray, primary, Barbes, Benigno, primary, Solorzano, Jose Luis, primary, Perez-Gracia, Jose Luis, primary, Labiano, Sara, primary, Sanmamed, Miguel F., primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Sanchez-Paulete, Alfonso R., primary, Aznar, M. Angela, primary, Rouzaut, Ana, primary, Schalper, Kurt A., primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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39. Supplementary Figure 6 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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40. Data from Agonist Anti-CD137 mAb Act on Tumor Endothelial Cells to Enhance Recruitment of Activated T Lymphocytes

Author

Palazón, Asís, primary, Teijeira, Alvaro, primary, Martínez-Forero, Iván, primary, Hervás-Stubbs, Sandra, primary, Roncal, Carmen, primary, Peñuelas, Iván, primary, Dubrot, Juan, primary, Morales-Kastresana, Aizea, primary, Pérez-Gracia, José Luis, primary, Ochoa, M. Carmen, primary, Ochoa-Callejero, Laura, primary, Martínez, Alfredo, primary, Luque, Alfonso, primary, Dinchuk, Joseph, primary, Rouzaut, Ana, primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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41. Supplementary Figures 1-5 from Agonist Anti-CD137 mAb Act on Tumor Endothelial Cells to Enhance Recruitment of Activated T Lymphocytes

Author

Palazón, Asís, primary, Teijeira, Alvaro, primary, Martínez-Forero, Iván, primary, Hervás-Stubbs, Sandra, primary, Roncal, Carmen, primary, Peñuelas, Iván, primary, Dubrot, Juan, primary, Morales-Kastresana, Aizea, primary, Pérez-Gracia, José Luis, primary, Ochoa, M. Carmen, primary, Ochoa-Callejero, Laura, primary, Martínez, Alfredo, primary, Luque, Alfonso, primary, Dinchuk, Joseph, primary, Rouzaut, Ana, primary, Jure-Kunkel, Maria, primary, and Melero, Ignacio, primary

Published
2023
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42. The last record of the last typotherid (Notoungulata, Mesotheriidae, Mesotherium cristatum) for the middle Pleistocene of the western Pampean region, Córdoba Province, Argentina, and its biostratigraphic implications

Author

Fernández-Monescillo, Marcos, primary, Martínez, Gastón, additional, García López, Daniel, additional, Frechen, Manfred, additional, Romero-Lebrón, Eugenia, additional, Krapovickas, Jerónimo M., additional, Haro, J. Augusto, additional, Rodríguez, Pablo E., additional, Rouzaut, Sabrina, additional, and Tauber, Adan A., additional

Published
2023
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43. Supplementary Figure 3 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 946K, Anti-CTLA-4 mAb treatment fails to extend survival of c-myc OVA tg+

Published
2023
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44. Supplementary Figure 7 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 953K, TILs recognize unknown antigens in JMJ cell lines.

Published
2023
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45. Supplementary Methods from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 129K

Published
2023
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46. Data from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

Purpose: Immunostimulatory monoclonal antibodies (ISmAb) that unleash antitumor immune responses are showing efficacy in cancer clinical trials. Anti-B7-H1 (PD-L1) monoclonal antibodies (mAb) block a critical inhibitory pathway in T cells, whereas anti-CD137 and OX40 mAbs provide T-cell costimulation. A combination of these ISmAbs (anti-CD137 + anti-OX40 + anti-B7-H1) was tested using a transgenic mouse model of multifocal and rapidly progressing hepatocellular carcinoma, in which c-myc drives transformation and cytosolic ovalbumin (OVA) is expressed in tumor cells as a model antigen.Experimental Design: Flow-cytometry and immunohistochemistry were used to quantify tumor-infiltrating lymphocytes (TIL) elicited by treatment and assess their activation status and cytolytic potential. Tolerance induction and its prevention/reversal by treatment with the combination of ISmAbs were revealed by in vivo killing assays.Results: The triple combination of ISmAbs extended survival of mice bearing hepatocellular carcinomas in a CD8-dependent fashion and synergized with adoptive T-cell therapy using activated OVA-specific TCR-transgenic OT-1 and OT-2 lymphocytes. Mice undergoing therapy showed clear increases in tumor infiltration by activated and blastic CD8+ and CD4+ T lymphocytes containing perforin/granzyme B and expressing the ISmAb-targeted receptors on their surface. The triple combination of ISmAbs did not result in enhanced OVA-specific cytotoxic T lymphocyte (CTL) activity but other antigens expressed by cell lines derived from such hepatocellular carcinomas were recognized by endogenous TILs. Adoptively transferred OVA-specific OT-1 lymphocytes into tumor-bearing mice were rendered tolerant, unless given the triple mAb therapy.Conclusion: Extension of survival and dense T-cell infiltrates emphasize the translational potential of combinational immunotherapy strategies for hepatocellular carcinoma. Clin Cancer Res; 19(22); 6151–62. ©2013 AACR.

Published
2023
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47. Supplementary figure 5 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Ignacio Melero, Maria Jure-Kunkel, Kurt A. Schalper, Ana Rouzaut, M. Angela Aznar, Alfonso R. Sanchez-Paulete, Elixabet Bolaños, Arantza Azpilikueta, Miguel F. Sanmamed, Sara Labiano, Jose Luis Perez-Gracia, Jose Luis Solorzano, Benigno Barbes, Saray Garasa, Inmaculada Rodriguez, and María E. Rodriguez-Ruiz

Abstract

single dose radiotherapy and hypofractionated doses increase the level of CD137 and PD-1 expression on the surface of tumor-infiltrating T cells.

Published
2023
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48. Supplementary figures and methods from Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy

Author

Ignacio Melero, Pedro Berraondo, David Sancho, Karmele Valencia, Vladislav Verkhusha, Ana Rouzaut, Inmaculada Rodriguez, Irene Olivera, Josune Egea, Steffanie K. Wculek, Arantza Azpilikueta, Assunta Cirella, Tsuneyasu Kaisho, Carmen Molina, Maria Gato, Carlos de Andrea, Carlos Luri-Rey, Saray Garasa, and Alvaro Teijeira

Abstract

Supplementary figures 1-5 Supplementary methods

Published
2023
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49. Supplementary Figure 6 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 2976K, HCC cell lines derived from c-myc OVA tg+ mice express OVA and functional antigen presenting molecules.

Published
2023
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50. Supplementary figure 3 from Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming

Author

Ignacio Melero, Maria Jure-Kunkel, Kurt A. Schalper, Ana Rouzaut, M. Angela Aznar, Alfonso R. Sanchez-Paulete, Elixabet Bolaños, Arantza Azpilikueta, Miguel F. Sanmamed, Sara Labiano, Jose Luis Perez-Gracia, Jose Luis Solorzano, Benigno Barbes, Saray Garasa, Inmaculada Rodriguez, and María E. Rodriguez-Ruiz

Abstract

Radiotherapy reduced the density and absolute numbers of CD4+, CD8+ and CD25+FOXP3+ T cells and Myeloid-derived suppressor cells both in the irradiated and non-irradiated lesions.

Published
2023
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