Extracellular K+ Dampens T Cell Functions in the Tumor Microenvironment
Description
Necrotic tumor cells release intracellular potassium [K+]i, raising extracellular K+ ([K+]e) in the tumor microenvironment (TME) to 40–50 mM (high-[K+]e). The template shows that high-[K+]e inhibited T-cell cytokine production and dampened cytotoxicity, by modulating the Akt signaling pathway. High-[K+]e also caused significant upregulation of immune checkpoint protein PD-1 in activated T cells. To this end, a novel KCa3.1 activator, SKA-346, rescued T cells from high-[K+]e mediated suppression.
Acknowledgements
References
Seow Theng Ong, Aik Seng Ng, Xuan Rui Ng, Zhong Zhuang, Brandon Han Siang Wong, Praseetha Prasannan, Yee Jiun Kok, Xuezhi Bi, Heesung Shim, Heike Wulff, Kanianthara George Chandy, and Navin Kumar Verma.Bioelectricity.Sep 2019.169-179. http://doi.org/10.1089/bioe.2019.0016
Eil, R., Vodnala, S., Clever, D. et al. Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature 537, 539–543 (2016). https://doi.org/10.1038/nature19364
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