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Hunting for clinical translation with innate-like immune cells and their receptors

Leukemia volume 28, pages 1181–1190 (2014)Cite this article

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Abstract

Allogeneic stem cell transplantation (allo-SCT) has so far been the most effective immunotherapy for hematological malignancies. However, it is becoming increasingly clear that the immunotherapeutic concepts underlying allo-SCT as well as the traditional dissection of the immune system into innate and adaptive arms need substantial refinement. More and more cell types migrate into the interface between innate and adaptive immunity, creating new terms such as innate-like lymphocytes. These innate-like cells, which include natural killer (NK) cells and γδT cells, could provide unique advantages to therapeutic interventions aimed at treating hematological malignancies, including protection against tumor relapse and viral infections without causing harmful graft-versus-host disease (GVHD). Recent molecular and conceptual insights into these subpopulations have opened new avenues to exploit their exciting features for the development of new compounds and to revisit current therapeutic standards in the treatment of hematological cancers. This review therefore aims to discuss the rapid progress in the understanding of molecular mechanisms by which NK cells and γδT cells recognize malignancies and viral infections, and the value of this increasing knowledge to complement the battle against life-threatening complications of current strategies to treat cancer.

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Acknowledgements

We thank Evelyn Ullrich for critical reading of the manuscript. This work was supported by grants of ZonMW 43400003, VIDI-ZonMW 917.11.337, LSBR 0902, AICR 10-736, and KWF UU-2010-4669.

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WS, CG, TS, ZS and JK wrote the manuscript; all authors agreed on the final manuscript.

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  1. Department of Hematology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    W Scheper, C Gründer, T Straetemans, Z Sebestyen & J Kuball

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  1. W Scheper
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  2. C Gründer
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  3. T Straetemans
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Correspondence to J Kuball.

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Competing interests

Clinical trials NTR2463 and NTR3079 were supported by Miltenyi Biotec.

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Scheper, W., Gründer, C., Straetemans, T. et al. Hunting for clinical translation with innate-like immune cells and their receptors. Leukemia 28, 1181–1190 (2014). https://doi.org/10.1038/leu.2013.378

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  • DOI: https://doi.org/10.1038/leu.2013.378

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