The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Ionic immune suppression within the tumour microenvironment limits T cell effector function
Open accessAbstract
Tumours progress despite being infiltrated by tumour-specific effector T cells. Tumours contain areas of cellular necrosis, which are associated with poor survival in a variety of cancers. Here, we show that necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours, causing profound suppression of T cell effector function. Elevation of the extracellular potassium concentration ([K+]e) impairs T cell receptor (TCR)-driven Akt–mTOR phosphorylation and effector programmes. Potassium-mediated suppression of Akt–mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A. Although the suppressive effect mediated by elevated [K+]e is independent of changes in plasma membrane potential (Vm), it requires an increase in intracellular potassium ([K+]i). Accordingly, augmenting potassium efflux in tumour-specific T cells by overexpressing the potassium channel Kv1.3 lowers [K+]i and improves effector functions in vitro and in vivo and enhances tumour clearance and survival in melanoma-bearing mice. These results uncover an ionic checkpoint that blocks T cell function in tumours and identify potential new strategies for cancer immunotherapy.
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Hodgkin, A. L., & Huxley, A. F. (1952) · The Journal of Physiology · doi:10.1113/jphysiol.1952.sp004764 · Cited by 23,191
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Cancer immunotherapy comes of age
Mellman, I., Coukos, G., & Dranoff, G. (2011) · Nature · doi:10.1038/nature10673 · Cited by 3,893
Potential, impedance, and rectification in membranes
Goldman, D. E. (1943) · Journal of General Physiology · doi:10.1085/jgp.27.1.37 · Cited by 2,777
Muñoz-Planillo, R., Kuffa, P., Martínez-Colón, G., Smith, B. L., Rajendiran, T. M., & Núñez, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.016 · Cited by 2,147
Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
Tran, E., Turcotte, S., Gros, A., Robbins, P. F., Lu, Y.-C., Dudley, M. E., Wunderlich, J. R., Somerville, R. P., Hogan, K., Hinrichs, C. S., et al. (2014) · Science · doi:10.1126/science.1251102 · Cited by 1,718
Self-citationRobbins, P. F., Morgan, R. A., Feldman, S. A., Yang, J. C., Sherry, R. M., Dudley, M. E., Wunderlich, J. R., Nahvi, A. V., Helman, L. J., Mackall, C. L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.2537 · Cited by 1,632
Self-citationMitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
Ho, P.-C., Bihuniak, J. D., Macintyre, A. N., Staron, M., Liu, X., Amezquita, R., Tsui, Y.-C., Cui, G., Micevic, G., Perales, J. C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.012 · Cited by 1,462
Cited by
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Approaches to treat immune hot, altered and cold tumours with combination immunotherapies
Galon, J., & Bruni, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0007-y · Cited by 3,409
Salt-responsive gut commensal modulates TH17 axis and disease
Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., Haase, S., Mähler, A., Balogh, A., Markó, L., et al. (2017) · Nature · doi:10.1038/nature24628 · Cited by 1,310
The Principles of Engineering Immune Cells to Treat Cancer
Lim, W. A., & June, C. H. (2017) · Cell · doi:10.1016/j.cell.2017.01.016 · Cited by 1,080
Metabolism of immune cells in cancer
Leone, R. D., & Powell, J. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-020-0273-y · Cited by 877
Metadata
- Authors
- Eil, R., Vodnala, S. K., Clever, D., Klebanoff, C. A., Sukumar, M., Pan, J. H., Palmer, D. C., Gros, A., Yamamoto, T. N., Patel, S. J., Guittard, G. C., Yu, Z., Carbonaro, V., Okkenhaug, K., Schrump, D. S., Linehan, W. M., Roychoudhuri, R., & Restifo, N. P.
- Venue
- Nature
- Published
- 2016-09-14
- Volume
- 537
- Issue
- 7621
- Pages
- 539-543
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2519107733
- Cited by
- 678
- References
- 40
- FWCI
- 27.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Eil, R., Vodnala, S. K., Clever, D., Klebanoff, C. A., Sukumar, M., Pan, J. H., Palmer, D. C., Gros, A., Yamamoto, T. N., Patel, S. J., Guittard, G. C., Yu, Z., Carbonaro, V., Okkenhaug, K., Schrump, D. S., Linehan, W. M., Roychoudhuri, R., & Restifo, N. P. (2016). Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature. https://doi.org/10.1038/nature19364
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
