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Innate lymphoid cells and cancer

Abstract

The innate lymphoid cell (ILC) family is composed of natural killer (NK) cells, ILC1, ILC2 and ILC3, which participate in immune responses to virus, bacteria, parasites and transformed cells. ILC1, ILC2 and ILC3 subsets are mostly tissue-resident, and are profoundly imprinted by their organ of residence. They exhibit pleiotropic effects, driving seemingly paradoxical responses such as tissue repair and, alternatively, immunopathology toward allergens and promotion of tumorigenesis. Despite this, a trickle of studies now suggests that non-NK ILCs may not be overwhelmingly tumorigenic and could potentially be harnessed to drive anti-tumor responses. Here, we examine the pleiotropic behavior of ILCs in cancer and begin to unravel the gap in our knowledge that exposes a new horizon for thinking about modifying ILCs and targeting them for immunotherapy.

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Fig. 1: The ILC family.
Fig. 2: ILCs and tumor immunity.

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Acknowledgements

This work was supported by grants and fellowships from the National Health and Medical Research Council (NHMRC) of Australia (APP1165443 to C. S., G. T. B. and E. V., and 1122277, 1054925, 1135898, 1123000 to G. T. B.), support from The University of Queensland Chair of Immunology (Diamantina Institute, G. T. B.), Cure Cancer Australia and Cancer Australia through the Cancer Australia Priority-driven Cancer Research Scheme (APP1163990 to N. J.) and Cancer Council NSW (RG21-05 G. T. B. and N. J.). The E.V. laboratory at CIML and Assistance-Publique des Hôpitaux de Marseille is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (TILC, grant agreement no. 694502 and MInfla-TILC, grant agreement no. 875102, MInfla-Tilc), the Agence Nationale de la Recherche including the PIONEER Project (ANR-17-RHUS-0007), MSDAvenir, Innate Pharma and institutional grants awarded to the CIML (INSERM, CNRS, and Aix-Marseille University) and Marseille Immunopole.

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Correspondence to Gabrielle T. Belz.

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E. V. is an employee of Innate Pharma. The other authors declare no competing interests.

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Nature Immunology thanks Sonia Tugues and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. 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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Jacquelot, N., Seillet, C., Vivier, E. et al. Innate lymphoid cells and cancer. Nat Immunol 23, 371–379 (2022). https://doi.org/10.1038/s41590-022-01127-z

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