Ton N. Schumacher is professor by special appointment at Leiden University Medical Center and principal investigator at The Netherlands Cancer Institute, Amsterdam, The Netherlands. In addition, Schumacher is member of the scientific advisory boards of the CIML (Marseille, France), the Champalimaud Foundation (Lisbon, Portugal), and the Berlin Immunology program (Berlin, Germany). Next to his academic activities, Schumacher is venture partner at Third Rock Ventures (Boston, USA). In his research, Schumacher aims to to dissect the activity of immune cells in human cancer and to use the resulting knowledge to develop novel cancer immunotherapies.

More information about Ton Schumacher

Cancer and the immune system

My overall research ambition has been to dissect how the human immune system can recognize cancer cells, and how such recognition can be strengthened for therapeutic purposes. To achieve this goal we employ a technology-driven approach, in which new assay systems are designed that can be used to determine how tumor-specific immune responses develop and are regulated. This technological toolbox is then exploited to reveal the mode of action of clinically used immunotherapies and to design more specific and more effective immune interventions. Some of the highlights of this work over the past decades have been the following

In early work, under guidance of Hidde Ploegh and in collaboration with amongst others Sjaak Neefjes, we developed technologies to measure which fragments from (tumor) antigens bind to MHC class I molecules and then utilized these technologies to describe the ligand preference of MHC molecules. Technologies developed in this work have subsequently been used widely to understand antigen recognition in both oncology, autoimmune disease, and infectious diseases (selected references: Schumacher, Cell 1990; Schumacher, Nature 1991).

We have provided the first in vivo proof of principle for the potential value of T cell receptor gene therapy to induce defined tumor-specific T cell responses; We’ve described potential safety issues, and described technology to develop collections of TCR genes that can be used for clinical development (selected references: Kessels, Nat Immunol 2001; Bendle, Nat Med 2010; Linnemann, Nat Med 2013; Strønen, Science 2016).

In more fundamental work, we ‘ve developed the concept of cellular barcoding to reveal single immune cell behavior in vivo and have used this technology to reveal fundamental aspects of immune responses and T cell memory (selected references: van Heijst, Science 2009; Naik, Nature 2013; Gerlach, Science 2013; Perié, Cell 2015).

In order to understand the antigen specificity of T cells that reside in human cancer lesions, we’ve developed high-throughput technology to measure T cell responses to tumor-associated antigens. In subsequent work, we have used these technologies to demonstrate that T cell responses against patient-specific mutation-derived antigens (‘neoantigens’) are common in melanoma patients and can be enhanced by immune checkpoint blockade, thereby explaining the preferential activity of these therapies in tumors with a high mutational burden, such as melanoma, NSCLC, and microsatellite-instable tumors (selected references: Toebes, Nat Med 2006; Hadrup, Nat Methods 2009; van Rooij, J Clin Oncol 2013; Rizvi, Science 2015; Linnemann, Nat Med 2015; Verdegaal, Nature 2016; Schumacher Ann Rev Immunol 2019).

Using genetic screening approaches, we have identified CMTM6 as a molecular partner of the PD-L1 T cell checkpoint and QPCTL as a post-translational modifier of the CD47 myeloid cell checkpoint. In addition, we demonstrated how small molecule inhibition of QPCTL can be used to promote control of tumor cells by macrophages and neutrophils. (references:  Mezzadra et al, Nature 2017, Logtenberg et al, Nat Med 2019).

In a clinical study together with Christian Blank, designed to directly compare the immune activating capacity of  immune checkpoint blockade given either prior to or following surgery, we demonstrated the superior immune activating capacity of neoadjuvant immune checkpoint blockade. These data, and the very high pathological response rates seen in this study and follow-up studies, provide a clear incentive for the broader clinical development of neoadjuvant cancer immunotherapy across cancer types (selected references: Blank, Nat Med 2018, Rozeman, Lancet Oncol 2019, Chalabi, Nat Med 2020).

Prizes and honourable appointments

1994-1996: Howard Hughes Medical Institute Fellow, The Life Sciences Research Foundation
2000: Pioneer Award 
2010: Amsterdam Inventor Award
2010: EMBO Member
2011: ERC AdG recipient
2012: SU2C Cancer Immunotherapy Dream Team Member
2013: Scientific Advisory Council, The Cancer Research Institute
2014: Fellow European Academy of Cancer Sciences
2014: Queen Wilhelmina Cancer Research Award
2014: San Salvatore Award
2015: Meyenburg Cancer Research Award
2016: W.B. Coley Award  
2016: van Loghem Award  
2016: Peter Speiser Award
2017: ERC AdG recipient 
2017: Academia Europaea Member
2017: Oncode Institute Member
2018: Honorary Member EATI
2019:ISI Highly cited researcher

Publications