Robbert (R. M.) Spaapen PhD


Immunology and Hemato-oncology


Novel strategies for identification and therapeutic application of minor histocompatibility antigens
Promotor: Prof H Lokhorst PhD
Co-promotor: T Mutis PhD
University of Utrecht

Research interests

We study the effects of intracellular protein expression, secreted proteins and chemical compounds on antigen presentation and costimulation on several immune and cancer-related cell types. Understanding and subsequent manipulation of antigen presentation and costimulation may generate therapeutic options for a wide variety of diseases.

All my research and some of my scientific interests can be captured by the following terms:

  • Basic and translational immunology
  • Immunology-related cell biology
  • Translational haemato-oncology
  • Translational melanoma immunology
  • Oncology-related microbiology

Research group: Antigen presentation and immunotherapy



  • Cell culture
  • Viral transduction
  • Flow Cytometry
  • Molecular biology techniques
  • mRNA analyses
  • In vivo immune responses
  • In vivo tumorigenesis
  • Database analyses
  • Basic bioinformatics


2013-present Group leader at the Dept of Immunopathology of Sanquin Research
2010-2013 Post-doctoral scientist at the Dept of Cell Biology II of The Netherlands Cancer Institute
2009-2010 Post-doctoral scientist at the Dept of Pathology of the University of Chicago
2005-2009 Research PhD student at the Dept of Clinical Chemistry and Haematology of the University Medical Center Utrecht
2000-2005 MSc Fundamental Biomedical Sciences at the University of Utrecht
1998-2000 Propaedeutic degrees Biology, Physics and Astronomy, Chemistry at the University of Utrecht

Other publications

Spranger S*, Spaapen RM*, Zha Y, Williams J, Meng Y, Gajewski TF. Upregulation of PD-L1, IDO and Tregs in the melanoma tumor microenvironment is driven by CD8+ T cells. Sci Transl Med 2013; 5(200):200ra116.* These authors contributed equally to this work

Gajewski TF, Woo SR, Zha Y, Spaapen R, Zheng Y, Corrales L, Spranger S. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol 2013; 25(2):268-76.

Zheng Y, Zha Y, Spaapen RM, Mathew R, Barr K, Bendelac A, Gajewski TF. Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy. Mol Immunol 2013; 55(3-4):283-91.

Oostvogels R, Minnema MC, van Elk M, Spaapen RM, Te Raa GD, Giovannone B, Buijs A, van Baarle D, Kater AP, Griffioen M, Spierings E, Lokhorst HM, Mutis T. Towards effective and safe immunotherapy after allogeneic stem cell transplantation: identification of hematopoietic-specific minor histocompatibility antigen UTA2-1. Leukemia 2013; 27(3):642-9.

Spaapen RM, Neefjes J. Immuno-waste exposure and further management. Nat Immunol 2012; 13(2):109-11.

Van der Poel CE, Spaapen RM, van de Winkel JGJ, Leusen JHW. Functional characteristics of the high affinity IgG receptor, FcγRI. J Immunol 2011; 186(5):2699-704.

Gajewski TF, Fuertes M, Spaapen R, Zheng Y, Kline J. Molecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment. Curr Opin Immunol 2011; 23(2):286-92.

Spaapen RM, Groen RWJ, van den Oudenalder K, Guichelaar T, van Elk M, Aarts-Riemens T, Bloem AC, Storm G, Martens AC, Lokhorst HM, Mutis T. Eradication of medullary multiple myeloma by CD4+ cytotoxic human T lymphocytes directed at a single minor histocompatibility antigen. Clin Cancer Res 2010; 16(22):5481-8.

Spaapen RM, de Kort RAL, van den Oudenalder K, van Elk M, Bloem AC, Lokhorst HM, Mutis T. Rapid identification of clinical relevant minor histocompatibility antigens via genome-wide zygosity-genotype correlation analysis. Clin Cancer Res 2009; 15(23):7137-43.

Spaapen RM, Lokhorst HM, van den Oudenalder K, Otterud BE, Dolstra H, Leppert MF, Minnema MC, Bloem AC, Mutis T. Toward targeting B cell cancers with CD4+ CTLs: identification of a CD19-encoded minor histocompatibility antigen using a novel genome-wide analysis. J Exp Med 2008; 205(12):2863-72.

Spaapen R, Mutis T. Targeting haematopoietic-specific minor histocompatibility antigens to distinguish graft-versus-tumour effects from graft-versus-host disease. Best Pract Res Clin Haematol 2008; 21(3):543-57.

Rozemuller H, van der Spek E, Bogers-Boer LH, Zwart MC, Verweij V, Emmelot M, Groen RW, Spaapen R, Bloem AC, Lokhorst HM, Mutis T, Martens AC. A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy. Haematologica 2008; 93(7):1049-57.

Spaapen R, van den Oudenalder K, Ivanov R, Bloem A, Lokhorst H, Mutis T. Rebuilding human leukocyte antigen class II-restricted minor histocompatibility antigen specificity in recall antigen-specific T cells by adoptive T cell receptor transfer: implications for adoptive immunotherapy. Clin Cancer Res 2007; 13(13):4009-15.

Hassink G, Kikkert M, van Voorden S, Lee SJ, Spaapen R, van Laar T, Coleman CS, Bartee E, Früh K, Chau V, Wiertz E. TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum. Biochem J 2005; 388(Pt 2):647-55.