Abstract
Alterations in key metabolic pathways are required for tumour development and the adaptation of tumour cells to intrinsic or extrinsic stresses, as well as for the regulation of immune cell fate and immune responses in the tumour microenvironment. In particular, the dysregulation or alteration of certain metabolites produced by tumour cells has been shown to be important in creating the immunosuppressive tumour microenvironment. Recent studies have broadened our understanding of the interactions between metabolites and antitumour immunity. Here we highlight how, beyond their metabolic role, metabolites can function as signalling molecules to modulate the behaviours of immune cells and tumour cells. We also discuss potential therapeutic strategies targeting specific metabolites and future research directions in metabolite sensing.
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Acknowledgements
The authors thank Z. Xia and Z. Li in the Jiang laboratory for assistance. This study was supported by the National Natural Science Foundation of China (grant nos. 82125030 and 82341022) to P.J., as well as by TsienTang Life Science Development Fund at Tsinghua University. Y.M. was supported by the Postdoctoral Innovation Talent Support Program, the National Natural Science Foundation of China (grant no. 82372824) and the Shuimu Tsinghua Scholar Program.
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P.J. conceived and conceptualized the review scope. Y.M. and W.X. reviewed the literature. Y.M., W.X. and P.J. created the initial versions of the figures. P.J., Y.M. and W.X. wrote the manuscript. P.J. supervised, revised and integrated the manuscript.
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Nature Reviews Immunology thanks Christian Frezza, who coreviewed with Desiree Schatton; Ping-Chih Ho; and Cheng-Chin Kuo for their contribution to the peer review of this work.
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Mao, Y., Xia, W. & Jiang, P. Metabolites as signalling molecules in the tumour immune microenvironment. Nat Rev Immunol (2026). https://doi.org/10.1038/s41577-025-01258-y
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DOI: https://doi.org/10.1038/s41577-025-01258-y
