REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1655730
This article is part of the Research TopicInterdisciplinary Innovations in CAR T-Cell Therapy for Autoimmune and Cancer TreatmentView all 4 articles
Innate Lymphoid Cells in the Spotlight: From Biomarkers to Blueprint for Innovative Immunotherapy
Provisionally accepted
- 1School of Biomedical Engineering, Faculty of Applied Science, University of British Columbia, Vancouver, British Columbia, Canada
- 2The University of British Columbia Michael Smith Laboratories, Vancouver, Canada
- 3Centre for Blood Research, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- 4Centre for Heart Lung Innovation, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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Here we provide a compendium on how innate lymphoid cells (ILCs) contribute to immune regulation, tissue homeostasis, and pathology across a range of autoimmune diseases and cancers. We highlight recent advances in understanding the functional diversity, plasticity, and tissue residency of ILC subsets-including their interactions with other immune and stromal cells-and their emerging roles as predictive, diagnostic, and therapeutic agents and targets.Particular attention is given to the regulatory potential and the cytotoxic functions of helper ILCs, and how these properties may be harnessed to therapeutic benefit. The manuscript identifies key challenges limiting the current clinical translation of ILC-based therapies and highlights promising technological developments including pluripotent stem cell (PSC)-derived ILC platforms, organoid models, and advanced single-cell profiling. It also proposes future pathways toward optimizing ILC-based immunotherapies, including engineering of chimeric antigen receptors (CARs) and chimeric switch receptors (CSRs), as well as cytokine modulation and immune checkpoint combinations. By integrating current insights with emerging concepts in cellular engineering and regenerative medicine, this review contributes to the conceptual foundation for developing next-generation precision immunotherapies. It will be of interest to immunologists, translational researchers, and clinicians working to advance cell-based treatments for cancer and immune-mediated diseases.
Keywords: ILCs as Biomarkers and Therapeutics min 5, max 8) Innate Lymphoid Cells (ILCs), Cancer, Autoimmune Diseases, biomarkers, Chronic inflammatory diseases, Immunotherapy, Regenerative Medicine
Received: 28 Jun 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Kuo, Brassard, Zandstra and Mcnagny. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kelly M Mcnagny, Centre for Blood Research, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, British Columbia, Canada
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.