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Flip the coin: IL-7 and IL-7R in health and disease

Nature Immunology volume 20, pages 1584–1593 (2019)Cite this article

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Abstract

The cytokine IL-7 and its receptor, IL-7R, are critical for T cell and, in the mouse, B cell development, as well as differentiation and survival of naive T cells, and generation and maintenance of memory T cells. They are also required for innate lymphoid cell (ILC) development and maintenance, and consequently for generation of lymphoid structures and barrier defense. Here we discuss the central role of IL-7 and IL-7R in the lymphoid system and highlight the impact of their deregulation, placing a particular emphasis on their ‘dark side’ as promoters of cancer development. We also explore therapeutic implications and opportunities associated with either positive or negative modulation of the IL-7–IL-7R signaling axis.

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Fig. 1: Atlas of IL-7 production.
Fig. 2: Developmental functions of IL-7.
Fig. 3: Potential mechanisms promoting outgrowth of leukemia cells in the context of IL-7 stimulation, which could explain how a limited resource such as IL-7 may benefit more (pre)leukemic cells than normal lymphoid precursors.
Fig. 4: Classes of IL7R gain-of-function mutants in leukemia.
Fig. 5: Potential pro-tumoral functions of IL-7R-mediated signaling in solid cancers.

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Acknowledgements

We thank M. Morre (Revimmune), R. Hotchkiss (Washington University), M. Cheever (University of Washington), R. Gress (NCI), I. Sereti (NIAID), N. Poirier (OSE Immunotherapeutics), C. Foley and A. Veradhachary (Fannin LLC) and E. Schafer (Baylor University) for sharing information on clinical trials, and M. Fernandes for help with draft figure preparation. J.T.B. is funded by the consolidator grant ERC CoG-648455 from the European Research Council, under the European Union’s Horizon 2020 research and innovation programme, and the FAPESP/20015/2014 and PTDC/MEC-HEM/31588/2017 grants from Fundação para a Ciência e a Tecnologia, Portugal; S.K.D. is funded by the intramural program of the US National Cancer Institute, National Institutes of Health, and the Children’s Cancer Foundation; B.S. is funded by the MRC (United Kingdom) under U117573801 and MR/P011225/1.

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Authors and Affiliations

  1. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

    João T. Barata

  2. Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, USA

    Scott K. Durum

  3. Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK

    Benedict Seddon

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J.T.B., S.K.D. and B.S. wrote the manuscript and approved its final version.

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Correspondence to João T. Barata.

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Competing interests

S.K.D. is a co-inventor on the patent application “IL-7R-alpha specific antibodies for treating acute lymphoblastic leukemia” filed by the NIH (DHHS). US Patent Application No. 62/238,612.

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Peer review information Zoltan Fehervari was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Barata, J.T., Durum, S.K. & Seddon, B. Flip the coin: IL-7 and IL-7R in health and disease. Nat Immunol 20, 1584–1593 (2019). https://doi.org/10.1038/s41590-019-0479-x

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