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The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies

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From Nature Immunology

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Abstract

Natural killer (NK) cells belong to the innate immune system and contribute to protecting the host through killing of infected, foreign, stressed or transformed cells. Additionally, via cellular cross-talk, NK cells orchestrate antitumor immune responses. Hence, significant efforts have been undertaken to exploit the therapeutic properties of NK cells in cancer. Current strategies in preclinical and clinical development include adoptive transfer therapies, direct stimulation, recruitment of NK cells into the tumor microenvironment (TME), blockade of inhibitory receptors that limit NK cell functions, and therapeutic modulation of the TME to enhance antitumor NK cell function. In this Review, we introduce the NK cell–cancer cycle to highlight recent advances in NK cell biology and to discuss the progress and problems of NK cell–based cancer immunotherapies.

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Fig. 1: Human and mouse NK cells.
Fig. 2: The NK cell–cancer cycle.
Fig. 3: Molecules that positively and negatively regulate the NK cell–cancer cycle.
Fig. 4

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Acknowledgements

T.B. was supported by a National Health and Medical Research Council (NHMRC) Early Career Research Fellowship (1138757) and Project Grant (1124690). M.J.S. was supported by a NHMRC Investigator Award (1173958) and Program Grant (1132519), a Cancer Research Institute CLIP grant and a Cancer Council of Queensland Project Grant (1140251). M.F.K. received NCI grants (1RO1 CA197363, UOI CA217864).

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  1. These authors jointly supervised this work: Mark J. Smyth and Kevin C. Barry.

Authors and Affiliations

  1. Oncology and Cellular Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

    Tobias Bald

  2. Department of Pathology, ImmunoX Initiative, and Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA

    Matthew F. Krummel

  3. Immunology of Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

    Mark J. Smyth

  4. Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Kevin C. Barry

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Correspondence to Mark J. Smyth or Kevin C. Barry.

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Competing interests

T.B. has research agreements with ENA Therapeutics and Bristol Myers Squibb and is on the scientific advisory board of Oncomyx. M.F.K. is a founder and shareholder of Pionyr Immunotherapeutics and has research agreements with Bristol Myers Squib, Eli Lilly, Pfizer, Amgen, Abbvie and Genentech. M.J.S. has research agreements with Bristol Myers Squibb and Tizona Therapeutics and is on the scientific advisory board of Tizona Therapeutics and Compass Therapeutics. K.C.B. declares no competing interests.

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Bald, T., Krummel, M.F., Smyth, M.J. et al. The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies. Nat Immunol 21, 835–847 (2020). https://doi.org/10.1038/s41590-020-0728-z

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