Abstract
The immune system has evolved intricate and sophisticated mechanisms to recognize and eliminate tumours. Among these, T helper 17 (TH17) cells seem to have a complex role in tumour immunity. Substantial evidence indicates that TH17 cells can impair the ability of immune cells to kill tumours, but growing research suggests that TH17 cells may also be crucial for facilitating effective antitumour immune responses. This apparent paradox is likely rooted, at least in part, in the remarkable plasticity of TH17 cells, which can adopt a range of effector functions depending on the environmental cues present in distinct tissue niches. Understanding the spectrum of functional adaptations that TH17 cells can undergo is especially important in cancer, where tumours exhibit substantial tissue heterogeneity. Here, we examine the context-dependent roles of TH17 cells in cancer, with a focus on the environmental signals and regulatory networks that may shape their phenotypes during cancer development and progression. Finally, we discuss how these insights could inform strategies to manipulate TH17 cells for the development of next-generation cancer immunotherapies.
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Acknowledgements
The authors are grateful to colleagues for collaboration and support. D.P. was supported by Cancer Research UK (CRUK) (grant C8142/A29069). A.B. and F.P. received support from the Wellcome Trust (grant 212240/Z/18/Z). F.P. was also supported by the Kennedy Trust for Rheumatology Research (grant KENN202115). M.P. was supported by the Medical Research Council (MRC) (grant MR/W025981/1).
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All authors contributed equally to the scope of the manuscript. D.P. and M.P. reviewed the literature, wrote the manuscript and designed the figures. D.P., A.B., F.P. and M.P. reviewed and edited the manuscript. F.P. and M.P. jointly supervised the work.
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F.P. has received research support from Janssen and Roche and consultancy fees from Genentech, GlaxoSmithKline (GSK) and Novartis. The other authors declare no competing interests.
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Pang, D., Bertocchi, A., Powrie, F. et al. Contextualizing TH17 cells in cancer. Nat Rev Immunol (2026). https://doi.org/10.1038/s41577-025-01250-6
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DOI: https://doi.org/10.1038/s41577-025-01250-6
