Dying Tumor Cells Release Potassium Ions That Inhibit Anti-Tumor Activity of T-Cells

Researchers at the National Cancer Institute (NCI) in the USA and the Babraham Institute in the UK have discovered how a mineral ion leaked from tumor tissue as it dies acts to stop the work of anti-tumor immune cells. This discovery provides a new approach in the development of treatments to engage the immune system in the fight against cancer. Tumors consist of a mix of actively multiplying cells and areas of dead tissue. Previous research has found that tumors can repress the immune cells that act against them but, until now, it wasn’t known how. New research, published online on September 14, 2016 in Nature, found that cells within tumors release potassium into the extracellular space upon dying. The article is titled: “Ionic Immune Suppression within the Tumour Microenvironment Limits T Cell Effector Function.” Potassium is an ion that is usually found at high concentrations within cells and not outside them. The increased level of potassium in the extracellular tumor environment dulled the activity of T cells, a specialized effector cell of the immune system, preventing their anti-tumor function. The researchers molecularly engineered tumor-specific T cells to increase their capacity to remove potassium from the cell. This created T cells that could effectively function to achieve an anti-tumor immune response despite the elevated potassium environment surrounding them. The cells were engineered to express more molecular pumps specifically to deport excess potassium from the cell. Boosting the cells’ “potassium export” capabilities prevented the high levels of intracellular potassium accumulation responsible for cellular dysfunction. Modifying the T cells in this way enhanced the clearance of tumors and survival rates in mice with skin cancer. Dr.
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