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Tackling the Achilles Heel of Immunotherapy: Validating imaging biomarkers and targeting the immunological niche of tumour hypoxia

Total Cost €


EC-Contrib. €






 HYPOXIMMUNO project word cloud

Explore the words cloud of the HYPOXIMMUNO project. It provides you a very rough idea of what is the project "HYPOXIMMUNO" about.

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Project "HYPOXIMMUNO" data sheet

The following table provides information about the project.


Organization address
address: Minderbroedersberg 4-6
postcode: 6200 MD

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 Netherlands [NL]
 Total cost 2˙499˙399 €
 EC max contribution 2˙499˙399 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-12-01   to  2021-11-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT MAASTRICHT NL (MAASTRICHT) coordinator 2˙402˙499.00


 Project objective

Lung cancer is the most common cause of death from cancer worldwide with 1.59 million deaths annually and it places the highest economic burden of all cancers on the EU at €18.8billion. These figures call for a major transformation of the therapeutic management of lung cancer. The recent developments in immunotherapy give new hope. At present a significant minority of patients benefit from immune therapy, which remains not curative when delivered alone. It is thus clear that improving the efficacy of immune therapy is needed as well as the identification of predictive biomarkers. Combining immunotherapy with radiotherapy improves effectiveness, but resistance is still common, most probably because of hypoxia. In HYPOXIMMUNO, we will open up a new paradigm in treating metastatic NSCLC. I will provide for the first time (pre)clinical proof of concept of (i) highly innovative CT-based radiomics and PET-hypoxia imaging patient stratification tools and (ii) a tri-modal curative hypoxia-targeting treatment strategy that complements current immunotherapy and radiotherapy approaches. This tri-modal curative treatment strategy is based on (1) high precision Stereotactic Radiotherapy (SABR) to kill cancer cells and trigger the immune system, combined with (2) a hypoxia-activated prodrug to target the hypoxic tumour cells resistant to immunotherapy and (3) a promising and innovative tumour specific antibody (Ab)-based immunotherapy (immunocytokine L19-IL2 to “push the accelerator” with or without a checkpoint inhibitor to “release the break”) to form a powerful synergistic immuno-oncology strategy. In HYPOXIMMUNO, I envision to lay the foundation for the next breakthrough in oncology, by improving patient selection and developing highly innovative cancer therapies that target hypoxia, to improve the quality of life and prolong survival of cancer patients, in particular patients with metastatic NSCLC (watch the animation summarising the project:


year authors and title journal last update
List of publications.
2019 Spiegelberg L., Van Hoof S.J., Biemans R., Lieuwes N.G., Marcus D., Niemans R., Theys J., Yaromina A., Lambin P., Verhaegen F., Dubois L.J.
Evofosfamide sensitizes esophageal carcinomas to radiation without increasing normal tissue toxicity.
published pages: , ISSN: 0167-8140, DOI:
Radiotherapy and Oncology 2020-01-29
2017 Aniek J.G. Even, Olga Hamming-Vrieze, Wouter van Elmpt, Véronique J.L. Winnepenninckx, Jolien Heukelom, Margot E.T. Tesselaar, Wouter V. Vogel, Ann Hoeben, Catharina M.L. Zegers, Daniëlle J. Vugts, Guus A.M.S. van Dongen, Harry Bartelink, Felix M. Mottaghy, Frank Hoebers, Philippe Lambin
Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.13910
Oncotarget 8/3 2020-01-29
2017 Evelyn E. C. de Jong, Wouter van Elmpt, Ralph T. H. Leijenaar, Otto S. Hoekstra, Harry J. M. Groen, Egbert F. Smit, Ronald Boellaard, Vincent van der Noort, Esther G. C. Troost, Philippe Lambin, Anne-Marie C. Dingemans
[18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches
published pages: 8-16, ISSN: 1619-7070, DOI: 10.1007/s00259-016-3498-y
European Journal of Nuclear Medicine and Molecular Imaging 44/1 2020-01-29
2017 Ana Ureba, Emely Lindblom, Alexandru Dasu, Johan Uhrdin, Aniek J. G. Even, Wouter van Elmpt, Philippe Lambin, Peter Wersäll, Iuliana Toma-Dasu
Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription
published pages: 485-490, ISSN: 0284-186X, DOI: 10.1080/0284186X.2017.1400177
Acta Oncologica 57/4 2020-01-29
2016 Ruben T. H. M. Larue, Lien Van De Voorde, Maaike Berbée, Wouter J. C. van Elmpt, Ludwig J. Dubois, Kranthi M. Panth, Sarah G. J. A. Peeters, Ann Claessens, Wendy M. J. Schreurs, Marius Nap, Fabiënne A. R. M. Warmerdam, Frans L. G. Erdkamp, Meindert N. Sosef, Philippe Lambin
A phase 1 ‘window-of-opportunity’ trial testing evofosfamide (TH-302), a tumour-selective hypoxia-activated cytotoxic prodrug, with preoperative chemoradiotherapy in oesophageal adenocarcinoma patients
published pages: , ISSN: 1471-2407, DOI: 10.1186/s12885-016-2709-z
BMC Cancer 16/1 2020-01-29
2017 Arthur Jochems, Issam El-Naqa, Marc Kessler, Charles S. Mayo, Shruti Jolly, Martha Matuszak, Corinne Faivre-Finn, Gareth Price, Lois Holloway, Shalini Vinod, Matthew Field, Mohamed Samir Barakat, David Thwaites, Dirk de Ruysscher, Andre Dekker, Philippe Lambin
A prediction model for early death in non-small cell lung cancer patients following curative-intent chemoradiotherapy
published pages: 226-230, ISSN: 0284-186X, DOI: 10.1080/0284186X.2017.1385842
Acta Oncologica 57/2 2020-01-29
2017 Ilke Tunali, Olya Stringfield, Albert Guvenis, Hua Wang, Ying Liu, Yoganand Balagurunathan, Philippe Lambin, Robert J. Gillies, Matthew B. Schabath
Radial gradient and radial deviation radiomic features from pre-surgical CT scans are associated with survival among lung adenocarcinoma patients
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.21629
Oncotarget 8/56 2020-01-29
2018 Jaap D. Zindler, Jacqueline Schiffelers, Philippe Lambin, Aswin L. Hoffmann
Improved effectiveness of stereotactic radiosurgery in large brain metastases by individualized isotoxic dose prescription: an in silico study
published pages: 560-569, ISSN: 0179-7158, DOI: 10.1007/s00066-018-1262-x
Strahlentherapie und Onkologie 194/6 2020-01-29
2018 Ralph TH Leijenaar, Marta Bogowicz, Arthur Jochems, Frank JP Hoebers, Frederik WR Wesseling, Sophie H Huang, Biu Chan, John N Waldron, Brian O\'Sullivan, Derek Rietveld, C Rene Leemans, Ruud H Brakenhoff, Oliver Riesterer, Stephanie Tanadini-Lang, Matthias Guckenberger, Kristian Ikenberg, Philippe Lambin
Development and validation of a radiomic signature to predict HPV (p16) status from standard CT imaging: a multicenter study
published pages: 20170498, ISSN: 0007-1285, DOI: 10.1259/bjr.20170498
The British Journal of Radiology 2020-01-29
2018 David A. Jaffray, Shiva Das, Paula M. Jacobs, Robert Jeraj, Philippe Lambin
How Advances in Imaging Will Affect Precision Radiation Oncology
published pages: 292-298, ISSN: 0360-3016, DOI: 10.1016/j.ijrobp.2018.01.047
International Journal of Radiation Oncology*Biology*Physics 101/2 2020-01-29
2017 Ruben T.H.M. Larue, Lien Van De Voorde, Janna E. van Timmeren, Ralph T.H. Leijenaar, Maaike Berbée, Meindert N. Sosef, Wendy M.J. Schreurs, Wouter van Elmpt, Philippe Lambin
4DCT imaging to assess radiomics feature stability: An investigation for thoracic cancers
published pages: 147-153, ISSN: 0167-8140, DOI: 10.1016/j.radonc.2017.07.023
Radiotherapy and Oncology 125/1 2020-01-29
2017 Patrick Grossmann, Olya Stringfield, Nehme El-Hachem, Marilyn M Bui, Emmanuel Rios Velazquez, Chintan Parmar, Ralph TH Leijenaar, Benjamin Haibe-Kains, Philippe Lambin, Robert J Gillies, Hugo JWL Aerts
Defining the biological basis of radiomic phenotypes in lung cancer
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.23421
eLife 6 2020-01-29
2017 Mathilda L. Bongers, Dirk de Ruysscher, Cary Oberije, Philippe Lambin, Carin A. Uyl-de Groot, José Belderbos, Veerle M.H. Coupé
published pages: 681-690, ISSN: 0266-4623, DOI: 10.1017/S0266462317000939
International Journal of Technology Assessment in Health Care 33/06 2020-01-29
2017 Evert J Van Limbergen, Dirk K De Ruysscher, Veronica Olivo Pimentel, Damiënne Marcus, Maaike Berbee, Ann Hoeben, Nicolle Rekers, Jan Theys, Ala Yaromina, Ludwig J Dubois, Philippe Lambin
Combining radiotherapy with immunotherapy: the past, the present and the future
published pages: 20170157, ISSN: 0007-1285, DOI: 10.1259/bjr.20170157
The British Journal of Radiology 90/1076 2020-01-29
2017 Janna E. van Timmeren, Ralph T.H. Leijenaar, Wouter van Elmpt, Bart Reymen, Cary Oberije, René Monshouwer, Johan Bussink, Carsten Brink, Olfred Hansen, Philippe Lambin
Survival prediction of non-small cell lung cancer patients using radiomics analyses of cone-beam CT images
published pages: 363-369, ISSN: 0167-8140, DOI: 10.1016/j.radonc.2017.04.016
Radiotherapy and Oncology 123/3 2020-01-29
2017 Janna E. van Timmeren, Ralph T. H. Leijenaar, Wouter van Elmpt, Bart Reymen, Philippe Lambin
Feature selection methodology for longitudinal cone-beam CT radiomics
published pages: 1537-1543, ISSN: 0284-186X, DOI: 10.1080/0284186X.2017.1350285
Acta Oncologica 56/11 2020-01-29
2017 Aniek J. G. Even, Bart Reymen, Matthew D. La Fontaine, Marco Das, Arthur Jochems, Felix M. Mottaghy, José S. A. Belderbos, Dirk De Ruysscher, Philippe Lambin, Wouter van Elmpt
Predicting tumor hypoxia in non-small cell lung cancer by combining CT, FDG PET and dynamic contrast-enhanced CT
published pages: 1591-1596, ISSN: 0284-186X, DOI: 10.1080/0284186X.2017.1349332
Acta Oncologica 56/11 2020-01-29
2017 Philippe Lambin, Jaap Zindler, Ben G.L. Vanneste, Lien Van De Voorde, Daniëlle Eekers, Inge Compter, Kranthi Marella Panth, Jurgen Peerlings, Ruben T.H.M. Larue, Timo M. Deist, Arthur Jochems, Tim Lustberg, Johan van Soest, Evelyn E.C. de Jong, Aniek J.G. Even, Bart Reymen, Nicolle Rekers, Marike van Gisbergen, Erik Roelofs, Sara Carvalho, Ralph T.H. Leijenaar, Catharina M.L. Zegers, Maria Jacobs, Janita van Timmeren, Patricia Brouwers, Jonathan A. Lal, Ludwig Dubois, Ala Yaromina, Evert Jan Van Limbergen, Maaike Berbee, Wouter van Elmpt, Cary Oberije, Bram Ramaekers, Andre Dekker, Liesbeth J. Boersma, Frank Hoebers, Kim M. Smits, Adriana J. Berlanga, Sean Walsh
Decision support systems for personalized and participative radiation oncology
published pages: 131-153, ISSN: 0169-409X, DOI: 10.1016/j.addr.2016.01.006
Advanced Drug Delivery Reviews 109 2020-01-29
2018 Davide Cusumano, Nicola Dinapoli, Luca Boldrini, Giuditta Chiloiro, Roberto Gatta, Carlotta Masciocchi, Jacopo Lenkowicz, Calogero Casà, Andrea Damiani, Luigi Azario, Johan Van Soest, Andre Dekker, Philippe Lambin, Marco De Spirito, Vincenzo Valentini
Fractal-based radiomic approach to predict complete pathological response after chemo-radiotherapy in rectal cancer
published pages: 286-295, ISSN: 0033-8362, DOI: 10.1007/s11547-017-0838-3
La radiologia medica 123/4 2020-01-29
2017 Arthur Jochems, Timo M. Deist, Issam El Naqa, Marc Kessler, Chuck Mayo, Jackson Reeves, Shruti Jolly, Martha Matuszak, Randall Ten Haken, Johan van Soest, Cary Oberije, Corinne Faivre-Finn, Gareth Price, Dirk de Ruysscher, Philippe Lambin, Andre Dekker
Developing and Validating a Survival Prediction Model for NSCLC Patients Through Distributed Learning Across 3 Countries
published pages: 344-352, ISSN: 0360-3016, DOI: 10.1016/j.ijrobp.2017.04.021
International Journal of Radiation Oncology*Biology*Physics 99/2 2020-01-29
2017 Evelyn E. C. de Jong, Wouter van Elmpt, Otto S. Hoekstra, Harry J. M. Groen, Egbert F. Smit, Ronald Boellaard, Philippe Lambin, Anne-Marie C. Dingemans
Quality assessment of positron emission tomography scans: recommendations for future multicentre trials
published pages: 1459-1464, ISSN: 0284-186X, DOI: 10.1080/0284186X.2017.1346824
Acta Oncologica 56/11 2020-01-29
2017 Ruben T. H. M. Larue, Janna E. van Timmeren, Evelyn E. C. de Jong, Giacomo Feliciani, Ralph T. H. Leijenaar, Wendy M. J. Schreurs, Meindert N. Sosef, Frank H. P. J. Raat, Frans H. R. van der Zande, Marco Das, Wouter van Elmpt, Philippe Lambin
Influence of gray level discretization on radiomic feature stability for different CT scanners, tube currents and slice thicknesses: a comprehensive phantom study
published pages: 1544-1553, ISSN: 0284-186X, DOI: 10.1080/0284186X.2017.1351624
Acta Oncologica 56/11 2020-01-29
2018 Sara Carvalho, Ralph T. H. Leijenaar, Esther G. C. Troost, Janna E. van Timmeren, Cary Oberije, Wouter van Elmpt, Lioe-Fee de Geus-Oei, Johan Bussink, Philippe Lambin
18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)-Radiomics of metastatic lymph nodes and primary tumor in non-small cell lung cancer (NSCLC) – A prospective externally validated study
published pages: e0192859, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0192859
PLOS ONE 13/3 2020-01-29
2017 Philippe Lambin, Ralph T.H. Leijenaar, Timo M. Deist, Jurgen Peerlings, Evelyn E.C. de Jong, Janita van Timmeren, Sebastian Sanduleanu, Ruben T.H.M. Larue, Aniek J.G. Even, Arthur Jochems, Yvonka van Wijk, Henry Woodruff, Johan van Soest, Tim Lustberg, Erik Roelofs, Wouter van Elmpt, Andre Dekker, Felix M. Mottaghy, Joachim E. Wildberger, Sean Walsh
Radiomics: the bridge between medical imaging and personalized medicine
published pages: 749-762, ISSN: 1759-4774, DOI: 10.1038/nrclinonc.2017.141
Nature Reviews Clinical Oncology 14/12 2020-01-29
2018 Sena Apeke, Laurent Gaubert, Nicolas Boussion, Philippe Lambin, Dimitris Visvikis, Vincent Rodin, Pascal Redou
Multi-Scale Modeling and Oxygen Impact on Tumor Temporal Evolution: Application on Rectal Cancer During Radiotherapy
published pages: 871-880, ISSN: 0278-0062, DOI: 10.1109/TMI.2017.2771379
IEEE Transactions on Medical Imaging 37/4 2020-01-29
2017 Timo M. Deist, A. Jochems, Johan van Soest, Georgi Nalbantov, Cary Oberije, Seán Walsh, Michael Eble, Paul Bulens, Philippe Coucke, Wim Dries, Andre Dekker, Philippe Lambin
Infrastructure and distributed learning methodology for privacy-preserving multi-centric rapid learning health care: euroCAT
published pages: 24-31, ISSN: 2405-6308, DOI: 10.1016/j.ctro.2016.12.004
Clinical and Translational Radiation Oncology 4 2020-01-29
2017 Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O’Connor, Corinne Faivre-Finn
Targeting Hypoxia to Improve Non–Small Cell Lung Cancer Outcome
published pages: 14-30, ISSN: 0027-8874, DOI: 10.1093/jnci/djx160
JNCI: Journal of the National Cancer Institute 110/1 2020-01-29

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