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Principal Investigator

Prof. J.E.M.A. (Reno) Debets, PhD

Head of Laboratory of Tumor Immunology

  • Department
  • Medical Oncology
  • Focus area
  • T-cell biology, T-cell treatmens, Molecular aspects of T-cell receptors
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Introduction

I chair the laboratory of Tumor Immunology, Dept Medical Oncology, Erasmus MC-Cancer Institute (since 2000). The laboratory consists of 18 people, including PhD students and postdoctoral fellows, and research aims to understand how solid tumors evade immune control, and to explore therapeutic strategies to (re-) establish tumor-specific T cell responses according to 3 lines: 

  • Develop and test adoptive T cell therapy
  • Understand and intervene with cross-talk between tumor cells and T cells
  • Monitor patient T cell immunity

Participations

I participate in the research groups of the Division of Onco-immunology and Department of Medical Oncology.

Current research projects

  • Treatment of melanoma and head-and-neck cancer patients with MAGE-C2-specific T cells
  • Adoptive T cell therapy to treat common cancers: new roads to unique targets and pre-treatments
  • Developing and testing combination immune therapies in preclinical models
  • Immunophenotyping of tumors and blood of patients

Field(s) of expertise

  • T cell biology and its shortcomings in tumors
  • T cell treatments, in particular adoptive T cell treatment
  • Molecular aspects of T cell receptors and gene-engineering of T cells
  • Tools to monitor T cell immunity in tumors and blood of patients

Education and career

I have received my MSc (1991, cum laude) in Biological Sciences, University of Maastricht, the Netherlands, and received my PhD (1996, cum laude) in the field of inflammation, Dept Immunology, Erasmus MC, Rotterdam, the Netherlands.

I have worked as a postdoctoral fellow for 3 years at DNAX Research Institute, Palo Alto, CA (currently part of Merck laboratories) in the field of immunology. I am a certified Immunologist (since 2005) and professor in T-cell immunity and adoptive therapy of tumors (since 2019).

Publications

A selection of publications (>125 manuscripts; H-index: 37)

1. Lamers CHJ, Sleijfer S, Vulto AG, Kruit WHJ, Kliffen M, Oosterwijk E, Debets R, Gratama JW, Stoter G. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol, 2006 24:e20.
2. Bendle G, Linnemann C, Hooijkaas A, de Witte M, Jorritsma A, Bies L, Kaiser A, Pouw N, Debets R, Song J-Y, Haanen J, Schumacher T. Lethal Graft-versus-Host Disease in mouse models of T cell receptor gene therapy. Nat Medicine, 2010 16:565.
3. Govers C, Sebestyén Z, Roszik J, van Brakel M, Berrevoets C, Szöőr A, Panoutsopoulou K, Broertjes M, Van T, Vereb G, Szöllősi J, Debets R. TCRs Genetically Linked to CD28 and CD3ε Do Not Mispair with Endogenous TCR Chains and Mediate Enhanced T Cell Persistence and Anti-Melanoma Activity. J Immunol, 2014 193:5315.
4. Straetemans T, Berrevoets C, Coccoris M, Treffers-Westerlaken E, Wijers R, Cole D, Dardalhon V, Sewell A, Taylor N, Verweij J, Debets R. Recurrence of melanoma following T cell treatment: continued antigen expression in a tumor that evades T cell recruitment. Mol Ther, 2015 23:396.
5. Debets R, Donnadieu E, Chouaib S, Coukos G. TCR-engineered T cells to treat tumors: seeing but not touching? Sem Immunol, 2016 28:10.
6. Smid M, Germán Rodríguez-González F, Sieuwerts AM, Salgado R, Prager-Van der Smissen WJC, van der Vlugt-Daane M, van Galen A, Nik-Zainal S, Staaf J, Brinkman AB, van de Vijver MJ, Richardson AL, Fatima A, Berentsen K, Butler A, Martin S, Davies HD, Debets R, Meijer-Van Gelder ME, van Deurzen CHM, MacGrogan G, van den Eynden GGM, Purdie C, Thompson AM, Caldas C, Span PN, Simpson PT, Lakhani SR, van Laere S, Desmedt C, Ringnér M, Tommasi S, Eyford J, Broeks A, Vincent-Salomon A, Futreal AP, Knappskog S, King T, Thomas G, Viari A, Langerod A, Børresen-Dale AL, Birney E, Stunnenberg HG, Stratton M, John A. Foekens JA, W.M. Martens JWM. Integration of the breast cancer genome and transcriptome associates specific mutational signatures with immune response. Nat Commun, 2016 7:12910.
7. Kunert A, Obenaus M, Lamers CH, Blankenstein T, Debets R. T cell receptors for clinical therapy: in vitro assessment of toxicity risk. Clin Cancer Res, 2017 23:6012.
8. Kolijn K, Verhoef E, Smid M, Bottcher R, Jenster G, Debets R, van Leenders G. Epithelial-mesenchymal transition in human prostate cancer demonstrates enhanced immune evasion marked by IDO1 expression. Cancer Res, 2018, 78:4671.
9. Hammerl D, Dietmar R, Martens J, Trajanowski Z, Debets R. Adoptive T Cell Therapy: New Avenues Leading to Safe Targets and Powerful Allies. Trends Immunol, 2018 18:30169.
10. Kunert A, Basak E, Hurkmans D, Klaver Y, van Brakel M, Oostvogels A, Lamers C, Bins S, Koolen S, van der Veldt A, Sleijfer S, Mathijssen R, Aerts J, Debets R. CD45RA+CCR7- CD8 T cells lacking co-stimulatory receptors demonstrate enhanced frequency in NSCLC patients responding to nivolumab. J ImmunoTherapy for Cancer, in press.

Teaching activities

I organise and lecture courses with a focus on T cell immunity and therapies (2 courses Molecular Medicine, since 2002; 1 course Infection and Immunity, since 2012; and 1 course Nanobiology, since 2018). I am faculty member of Post Graduate Schools (Molecular Medicine and Infection and Immunity, since 2012); departmental coordinator of research internships (curriculum medicine, since 2016); and departmental coordinator of annual research meetings for PhD students (since 2014). I supervise and guide individual research projects of PhDs (completed and ongoing co-promotorships: 14), clinical fellows and bachelor and master students (>40). In addition, I have been educational officer of an Innovative Training Network, an H2020 Marie Sklodowska Curie action (organizing workshops/courses for 12 international PhD students, 2010-2013).

Lastly, I participate in (inter)national thesis defence committees; and give international lectures per invitation as well as workshops for clinical specialists.


Other positions

I have initiated the Erasmus MC ‘Tumor Immunology Platform’ where bachelor, master, PhD students, postdoctoral fellows and PIs from multiple departments weekly discuss papers and projects (since 2012), and which is now integrated into the ACE ‘Tumor Immunology and Immune Therapy’ (chair of ACE since 2016). I am a member of steering committees overseeing inter-departmental efforts to immune-profile blood and tumors of patients with various tumors treated with standard or experimental therapies (acronyms: Multomab; Responder; Impa). In addition, I give scientific advice to: ‘Institut National du Cancer’, Paris, France (member in 2016; chair in 2017); International Society for Cellular Therapy against Cancer (2006-2010); and Dutch Society of Immunology (2019-2020). Also, I review for international journals, well as (inter)national research grant applications. And I have been a member of organizing committees of Cellular Therapy of Cancer Symposia in 2006 (Manchester), 2009 (Milan), 2010 (Montpellier) and 2013 (London).

Scholarships, grants, and awards

I have been awarded the Erasmus MC’s Research Award for PhD thesis (1997). And I have acquired multiple grants from World Cancer Research (2016), EU (2006, 2010, 2012), Dutch Cancer Society (2008, 2011, 2014, 2015, 2018), Holland Health TKI (2017) and others, culminating in 6.5 M€ of awarded research grants (primary applicant: 5,3 M€) (since 2006).

More

Milestones of our laboratory:

The laboratory’s research resulted in phase I/II studies to assess the activity of gene-engineered T cells in advanced renal cell cancer, the first clinical study of its nature in Europe (completed); and advanced melanoma and head-and-neck carcinoma (scheduled for Q4 2019). Furthermore, translational research resulted in the selection of new targets and T cell receptors as well as strategies to sensitize tumors to T cell treatments (which are currently under development). In addition, immune profiling using multiplex technologies of large cohorts of patients with various tumors and treated with standard or experimental therapies revealed potentially new predictive immune markers.