SENSIT SIGNED
Sensitivity of human tumors to T cell attack
Total Cost €
0EC-Contrib. €
0Partnership
0Views
0SENSIT project word cloud
Explore the words cloud of the SENSIT project. It provides you a very rough idea of what is the project "SENSIT" about.
Project "SENSIT" data sheet
The following table provides information about the project.
| Coordinator |
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Project website | https://www.nki.nl/divisions/molecular-oncology-immunology/schumacher-t-group/ |
| Total cost | 2˙405˙625 € |
| EC max contribution | 2˙405˙625 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2016-ADG |
| Funding Scheme | ERC-ADG |
| Starting year | 2017 |
| Duration (year-month-day) | from 2017-12-01 to 2022-11-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS | NL (AMSTERDAM) | coordinator | 2˙405˙625.00 |
Map
Project objective
The goal of this project is to describe the tumor cell-intrinsic mechanisms that determine whether ‘foreign’ human cancers are sensitive or resistant to the tumor-specific T cell response they induce. In this effort, I will focus on 3 linked questions:
1). While we know that T cell activity in human tumors can lead to cancer regression, we do not know whether such regression is mostly mediated by T cell secreted cytokines or granzyme mediated lysis. We will address this fundamental question by analysis of the sensitivity of human tumors to defined T cell effector mechanisms, and subsequent correlation to patient outcome upon immunotherapeutic intervention.
2). We will complement this analysis of baseline tumor sensitivity with a systematic analysis of acquired immunotherapy resistance in patients treated with T cell checkpoint blockade. Through comparative genomic and immunological analysis of pre- and post-therapy tumors we will determine the clinical importance of tumor cell-intrinsic mechanisms of acquired resistance, and will identify novel mechanisms of such resistance.
3). In addition to these unbiased analyses of tumor resistance, we will focus on one resistance pathway of particular interest: Expression of PD-L1 has emerged as the key immune inhibitory pathway in human cancers, but our understanding of PD-L1 protein regulation is highly limited. We have recently identified PD-L1M1 as a molecular partner of PD-L1 that controls its cell surface abundance. A central goal of this application is to understand the function of the PD-L1 – PD-L1M1 complex, and whether PD-L1M1 can be used as a target for immunotherapeutic interventions.
Collectively, this project exploits three approaches to reach one goal: fundamental insight into the mechanisms that control the sensitivity of human cancers to T cell attack. In addition to the mechanistic insights we will obtain, this project may yield novel strategies to enhance tumor-specific T cell activity in patients.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Meike E. W. Logtenberg, J. H. Marco Jansen, Matthijs Raaben, Mireille Toebes, Katka Franke, Arianne M. Brandsma, Hanke L. Matlung, Astrid Fauster, Raquel Gomez-Eerland, Noor A. M. Bakker, Simone van der Schot, Koen A. Marijt, Martijn Verdoes, John B. A. G. Haanen, Joost H. van den Berg, Jacques Neefjes, Timo K. van den Berg, Thijn R. Brummelkamp, Jeanette H. W. Leusen, Ferenc A. Scheeren, Ton N. S Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy published pages: 612-619, ISSN: 1078-8956, DOI: 10.1038/s41591-019-0356-z |
Nature Medicine 25/4 | 2019-11-12 |
| 2018 |
Daniela S. Thommen, Viktor H. Koelzer, Petra Herzig, Andreas Roller, Marcel Trefny, Sarah Dimeloe, Anna Kiialainen, Jonathan Hanhart, Catherine Schill, Christoph Hess, Spasenija Savic Prince, Mark Wiese, Didier Lardinois, Ping-Chih Ho, Christian Klein, Vaios Karanikas, Kirsten D. Mertz, Ton N. Schumacher, Alfred Zippelius A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade published pages: 994-1004, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0057-z |
Nature Medicine 24/7 | 2019-06-11 |
| 2017 |
Riccardo Mezzadra, Chong Sun, Lucas T. Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Meike E. W. Logtenberg, Maarten Slagter, Elisa A. Rozeman, Ingrid Hofland, Annegien Broeks, Hugo M. Horlings, Lodewyk F. A. Wessels, Christian U. Blank, Yanling Xiao, Albert J. R. Heck, Jannie Borst, Thijn R. Brummelkamp, Ton N. M. Schumacher Identification of CMTM6 and CMTM4 as PD-L1 protein regulators published pages: 106-110, ISSN: 0028-0836, DOI: 10.1038/nature23669 |
Nature 549/7670 | 2019-06-11 |
| 2018 |
Chong Sun, Riccardo Mezzadra, Ton N. Schumacher Regulation and Function of the PD-L1 Checkpoint published pages: 434-452, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2018.03.014 |
Immunity 48/3 | 2019-06-11 |
| 2019 |
Hanjie Li, Anne M. van der Leun, Ido Yofe, Yaniv Lubling, Dikla Gelbard-Solodkin, Alexander C.J. van Akkooi, Marlous van den Braber, Elisa A. Rozeman, John B.A.G. Haanen, Christian U. Blank, Hugo M. Horlings, Eyal David, Yael Baran, Akhiad Bercovich, Aviezer Lifshitz, Ton N. Schumacher, Amos Tanay, Ido Amit Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma published pages: 775-789.e18, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.11.043 |
Cell 176/4 | 2019-06-11 |
| 2018 |
Daniela S. Thommen, Ton N. Schumacher T Cell Dysfunction in Cancer published pages: 547-562, ISSN: 1535-6108, DOI: 10.1016/j.ccell.2018.03.012 |
Cancer Cell 33/4 | 2019-06-11 |
| 2019 |
Meike E. W. Logtenberg, J. H. Marco Jansen, Matthijs Raaben, Mireille Toebes, Katka Franke, Arianne M. Brandsma, Hanke L. Matlung, Astrid Fauster, Raquel Gomez-Eerland, Noor A. M. Bakker, Simone van der Schot, Koen A. Marijt, Martijn Verdoes, John B. A. G. Haanen, Joost H. van den Berg, Jacques Neefjes, Timo K. van den Berg, Thijn R. Brummelkamp, Jeanette H. W. Leusen, Ferenc A. Scheeren, Ton N. Schumacher Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy published pages: 612-619, ISSN: 1078-8956, DOI: 10.1038/s41591-019-0356-z |
Nature Medicine 25/4 | 2019-06-11 |
| 2018 |
Krijn K. Dijkstra, Chiara M. Cattaneo, Fleur Weeber, Myriam Chalabi, Joris van de Haar, Lorenzo F. Fanchi, Maarten Slagter, Daphne L. van der Velden, Sovann Kaing, Sander Kelderman, Nienke van Rooij, Monique E. van Leerdam, Annekatrien Depla, Egbert F. Smit, Koen J. Hartemink, Rosa de Groot, Monika C. Wolkers, Norman Sachs, Petur Snaebjornsson, Kim Monkhorst, John Haanen, Hans Clevers, Ton N. Schumacher, Emile E. Voest Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids published pages: 1586-1598.e12, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.07.009 |
Cell 174/6 | 2019-06-11 |
Are you the coordinator (or a participant) of this project? Plaese send me more information about the "SENSIT" project.
For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.
Send me an email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.
Thanks. And then put a link of this page into your project's website.
The information about "SENSIT" are provided by the European Opendata Portal: CORDIS opendata.