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Selected biological issues affecting relapse after stem cell transplantation: role of T-cell impairment, NK cells and intrinsic tumor resistance

Bone Marrow Transplantation volume 53, pages 949–959 (2018)Cite this article

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Abstract

The graft vs. leukemia (GvL) effect as a method of preventing relapse is well described after allogeneic hematopoietic cell transplantation (HCT), but the mechanisms to this effect and how tumor sometimes develops resistance to GvL are just beginning to be understood. This article reviews and expands upon data presented at the Third International Workshop on Biology, Prevention and Treatment of Relapse after Stem Cell Transplantation held in Hamburg, Germany, in November 2016. We first discuss in detail the role that T-cell impairment early after HCT plays in relapse by looking at data from T cell-depleted approaches as well as the clear role that early T-cell recovery has shown in improving outcomes. We then review key findings regarding the role of specific KIR donor/recipient pairings that contribute to relapse prevention after HCT for several tumor types. Finally, we discuss a unique mouse model following the development of tumor resistance to GvL. Detailed molecular characterization of events marking the development of tumor resistance to the immunotherapy of GvL may help in developing future strategies to overcome immune escape.

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Acknowledgements

The work of MvdB was supported by the National Institutes of Health award numbers R01-HL069929 (MvdB), R01-AI101406 (MvdB), P01-CA023766 (RJ O’Reilly) and Project 4 of P01-CA023766 (MvdB). Support was also received from The Lymphoma Foundation, The Susan and Peter Solomon Divisional Genomics Program, Cycle for Survival and P30 CA008748 MSK Cancer Center Support Grant/Core Grant. The work of MU was supported by the Deutsche Krebshilfe e.V. (project 110351) and the research commission of the Medical faculty of the Heinrich Heine University. The work of LJ was supported by the European Molecular Biology Organization (EMBO; ALTF 431-2017) and the MSK Sawiris Foundation Myeloma and Transplant Research Award. The work of MAP was supported by 2UG1HL069254-17 (NHLBI/NCI), R01 CA181050 (NCI), R34HL133384 (NHLBI) and U01AI126612 (NIAID), and by the Johnny Crisstopher Children’s Charitable Foundation St. Baldrick’s Consortium Grant.

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    Authors and Affiliations

    1. Center of Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA

      Marcel van den Brink

    2. Institute for Transplantation Diagnostics and Cell Therapeutics, University Clinic Düsseldorf, Düsseldorf, Germany

      Markus Uhrberg

    3. Department of Medicine and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

      Lorenz Jahn

    4. Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA

      John F. DiPersio

    5. Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, USA

      Michael A. Pulsipher

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    1. Marcel van den Brink
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    2. Markus Uhrberg
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    3. Lorenz Jahn
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    4. John F. DiPersio
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    5. Michael A. Pulsipher
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    Corresponding author

    Correspondence to Michael A. Pulsipher.

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    Conflict of interest

    Marcel van den Brink: current: research support: Seres; past 2 years: consultant for Jazz Pharmaceuticals, Novartis, Regeneron, Flagship Ventures, Boehringer Ingelheim, Merck and Evelo. John F DiPersio: stock/equity/founder: Magenta, Boston; honorarium: Celgene, Macrogenics; consultant for Zymeworks, Incyte and Celgene. Michael A Pulsipher: advisory board: Novartis, Adaptive, Chimerix and CLS Behring; educational meetings for Jazz, Medac and Amgen.

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    Marcel van den Brink, Markus Uhrberg, Lorenz Jahn, John F. DiPersio and Michael A. Pulsipher contributed equally to this work.

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    van den Brink, M., Uhrberg, M., Jahn, L. et al. Selected biological issues affecting relapse after stem cell transplantation: role of T-cell impairment, NK cells and intrinsic tumor resistance. Bone Marrow Transplant 53, 949–959 (2018). https://doi.org/10.1038/s41409-017-0078-0

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