Cancer cells often rely on glycolysis for energy metabolism. Increased glycolysis leads to the increased production of lactate and H+ ions, which should hypothetically lower intracellular pH. However, we find that tumor cells combat intracellular over-acidification by synthesizing carnosine, especially under hypoxic conditions, which allows them to control lysosome-dependent galectin-9 expression and evade T cell-mediated immune surveillance.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Casey, J. R. et al. Sensors and regulators of intracellular pH. Nat. Rev. Mol. Cell Biol. 11, 50–61 (2010). A review article that discusses different proteins and metabolites specialized to sense or regulate intracellular pH.
Vaughan-Jones, R. D. et al. Intrinsic H+ ion mobility in the rabbit ventricular myocyte. J. Physiol. 541, 139–158 (2002). This paper reports the sources of intrinsic mobile buffers and their working mechanism.
Oginuma, M. et al. Intracellular pH controls WNT downstream of glycolysis in amniote embryos. Nature 584, 98–101 (2020). This paper reports that intracellular pH controls the development of amniote embryos by regulating the WNT pathway.
Reddy, A. et al. pH-gated succinate secretion regulates muscle remodeling in response to exercise. Cell 183, 62–75 (2020). This paper reports that muscle tissue adaptation to exercise is regulated by a bioenergetic sensor that uses pH and succinate.
Heuser, J. Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. J. Cell Biol. 108, 855–864 (1989). This paper reports that lysosomal subcellular distribution is regulated by intracellular pH.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Yan, R. et al. Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion. Nature https://doi.org/10.1038/s41590-023-01719-3 (2024).
Rights and permissions
About this article
Cite this article
Carnosine helps cancer cells to evade immune surveillance by regulating intracellular pH. Nat Immunol 25, 399–400 (2024). https://doi.org/10.1038/s41590-023-01740-6
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41590-023-01740-6
