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Immune-senescence SIGNED

Dual targeting of senescence and tumor immunity for cancer therapy

Total Cost €

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EC-Contrib. €

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Partnership

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Project "Immune-senescence" data sheet

The following table provides information about the project.

Coordinator
FONDAZIONE PER L'ISTITUTO ONCOLOGICO DI RICERCA (IOR) 

Organization address
address: VIA VINCENZO VELA 6
city: BELLINZONA
postcode: 6500
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FONDAZIONE PER L'ISTITUTO ONCOLOGICO DI RICERCA (IOR) CH (BELLINZONA) coordinator 2˙000˙000.00

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 Project objective

We have previously demonstrated that cellular senescence opposes tumorigenesis thereby opening up new potential opportunities for cancer treatment. Senescence and tumor immunity in cancer are tightly interconnected. Tumor-infiltrating immune cells promote the clearance of senescent tumor cells thereby contributing to the tumor suppressive function of senescence. Moreover, T lymphocytes can drive senescence in cancers by secreting different cytokines in the tumor microenvironment. We have also recently reported that GR1 myeloid cells antagonize treatment-induced senescence (TIS) and that compounds that block the tumor recruitment of GR1 cells enhance TIS. Major objective of this proposal is to characterize the immune landscape of different prostate cancer mouse models in order to develop novel treatment modalities that combine pro-senescence compounds with immunotherapy. Using proteomics and bioinformatics approaches, we will assess how the genetic background of prostate tumors, shapes the tumor microenvironment and immune response during TIS. Next, we will define the mechanisms that regulate the recruitment and activation of myeloid derived suppressive cells, macrophages and B-lymphocytes in Pten deficient prostate tumors by focusing on a novel class of secreted factors identified in these tumors. We will also assess in vivo whether the secretome of tumor cells can transmit senescence to TILs and compounds that interfere with the secretome can prevent immunosenescence. Finally, we will develop monoclonal antibodies directed towards senescent tumors cells that we will use as diagnostic and therapeutic tools. These antibodies will be used as biomarkers to detect senescent tumor cells in prostate cancers and will be tested in pre-clinical trials to assess whether they improve tumor clearance during TIS. Our findings will form the basis for future clinical trials in prostate cancer patients.

 Publications

year authors and title journal last update
List of publications.
2019 Arianna Calcinotto, Jaskaren Kohli, Elena Zagato, Laura Pellegrini, Marco Demaria, Andrea Alimonti
Cellular Senescence: Aging, Cancer, and Injury
published pages: 1047-1078, ISSN: 0031-9333, DOI: 10.1152/physrev.00020.2018
Physiological Reviews 99/2 2019-07-25
2017 Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Natalia Martín-Martín, Sonia Fernandez-Ruiz, James D. Sutherland, Michelle Clasquin, Julen Tomas-Cortazar, Jose Jimenez, Ines Torres, Phong Quang, Pilar Ximenez-Embun, Ruzica Bago, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Isabel Lacasa-Viscasillas, Miguel Unda, Verónica Torrano, Diana Cabrera, Sebastiaan M. van Liempd, Ylenia Cendon, Elena Castro, Stuart Murray, Ajinkya Revandkar, Andrea Alimonti, Yinan Zhang, Amelia Barnett, Gina Lein, David Pirman, Ana R. Cortazar, Leire Arreal, Ludmila Prudkin, Ianire Astobiza, Lorea Valcarcel-Jimenez, Patricia Zuñiga-García, Itziar Fernandez-Dominguez, Marco Piva, Alfredo Caro-Maldonado, Pilar Sánchez-Mosquera, Mireia Castillo-Martín, Violeta Serra, Naiara Beraza, Antonio Gentilella, George Thomas, Mikel Azkargorta, Felix Elortza, Rosa Farràs, David Olmos, Alejo Efeyan, Juan Anguita, Javier Muñoz, Juan M. Falcón-Pérez, Rosa Barrio, Teresa Macarulla, Jose M. Mato, Maria L. Martinez-Chantar, Carlos Cordon-Cardo, Ana M. Aransay, Kevin Marks, José Baselga, Josep Tabernero, Paolo Nuciforo, Brendan D. Manning, Katya Marjon, Arkaitz Carracedo
mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer
published pages: 109-113, ISSN: 0028-0836, DOI: 10.1038/nature22964
Nature 547/7661 2019-07-25
2016 Ajinkya Revandkar, Maria Luna Perciato, Alberto Toso, Abdullah Alajati, Jingjing Chen, Hermeto Gerber, Mitko Dimitrov, Andrea Rinaldi, Nicolas Delaleu, Emiliano Pasquini, Rocco D’Antuono, Sandra Pinton, Marco Losa, Letizia Gnetti, Alberto Arribas, Patrick Fraering, Francesco Bertoni, Alain Nepveu, Andrea Alimonti
Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence
published pages: , ISSN: 2041-1723, DOI: 10.1038/ncomms13719
Nature Communications 7/1 2019-07-25
2018 Jacopo Sgrignani, JingJing Chen, Andrea Alimonti, Andrea Cavalli
How phosphorylation influences E1 subunit pyruvate dehydrogenase: A computational study
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-33048-z
Scientific Reports 8/1 2019-07-25
2018 Daniel Nava Rodrigues, Pasquale Rescigno, David Liu, Wei Yuan, Suzanne Carreira, Maryou B. Lambros, George Seed, Joaquin Mateo, Ruth Riisnaes, Stephanie Mullane, Claire Margolis, Diana Miao, Susana Miranda, David Dolling, Matthew Clarke, Claudia Bertan, Mateus Crespo, Gunther Boysen, Ana Ferreira, Adam Sharp, Ines Figueiredo, Daniel Keliher, Saud Aldubayan, Kelly P. Burke, Semini Sumanasuriya, Mariane Sousa Fontes, Diletta Bianchini, Zafeiris Zafeiriou, Larissa Sena Teixeira Mendes, Kent Mouw, Michael T. Schweizer, Colin C. Pritchard, Stephen Salipante, Mary-Ellen Taplin, Himisha Beltran, Mark A. Rubin, Marcin Cieslik, Dan Robinson, Elizabeth Heath, Nikolaus Schultz, Joshua Armenia, Wassim Abida, Howard Scher, Christopher Lord, Alan D’Andrea, Charles L. Sawyers, Arul M. Chinnaiyan, Andrea Alimonti, Peter S. Nelson, Charles G. Drake, Eliezer M. Van Allen, Johann S. de Bono
Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer
published pages: 5185-5185, ISSN: 0021-9738, DOI: 10.1172/jci125184
Journal of Clinical Investigation 128/11 2019-07-25
2018 Arianna Calcinotto, Clarissa Spataro, Elena Zagato, Diletta Di Mitri, Veronica Gil, Mateus Crespo, Gaston De Bernardis, Marco Losa, Michela Mirenda, Emiliano Pasquini, Andrea Rinaldi, Semini Sumanasuriya, Maryou B. Lambros, Antje Neeb, Roberta Lucianò, Carlo A. Bravi, Daniel Nava-Rodrigues, David Dolling, Tommaso Prayer-Galetti, Ana Ferreira, Alberto Briganti, Antonio Esposito, Simon Barry, Wei Yuan, Adam Sharp, Johann de Bono, Andrea Alimonti
IL-23 secreted by myeloid cells drives castration-resistant prostate cancer
published pages: 363-369, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0266-0
Nature 559/7714 2019-07-25
2018 Jingjing Chen, Ilaria Guccini, Diletta Di Mitri, Daniela Brina, Ajinkya Revandkar, Manuela Sarti, Emiliano Pasquini, Abdullah Alajati, Sandra Pinton, Marco Losa, Gianluca Civenni, Carlo V. Catapano, Jacopo Sgrignani, Andrea Cavalli, Rocco D’Antuono, John M. Asara, Andrea Morandi, Paola Chiarugi, Sara Crotti, Marco Agostini, Monica Montopoli, Ionica Masgras, Andrea Rasola, Ramon Garcia-Escudero, Nicolas Delaleu, Andrea Rinaldi, Francesco Bertoni, Johann de Bono, Arkaitz Carracedo, Andrea Alimonti
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer
published pages: 219-228, ISSN: 1061-4036, DOI: 10.1038/s41588-017-0026-3
Nature Genetics 50/2 2019-07-25

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