T cells are responsible for defending against pathogen infection, tumorigenesis, and are the primary cells mobilized by tumor immunotherapy. But cancer cells have a variety of tricks at their disposal to evade immune screening and attack.
How to make immune cells more active and promote the efficacy of tumor immunotherapy?
Scientists from the national cancer institute found that dying cancer cells release potassium ions, a compound in high concentrations that can damage T cells' metabolism and nutritional intake, causing them to go hungry and strike.
But, amazingly, high levels of potassium also alter the epigenetic modifications of t-cells, keeping them "stem cell like." In other words, in a tumor, these stem cell-like T cells just keep reproducing themselves, but fail to differentiate and mature into killer T cells.
This means that even if T cells were present, the tumour would not be attacked because of its "stem cell nature" and would continue to grow.
The researchers speculate that using this "stem cell property" could improve the effectiveness of cancer immunotherapy.
Currently, immunotherapy has brought positive hope to cancer patients, especially some patients with advanced stage achieved complete remission. But the cancer immunotherapy response rate is only 25 to 30 percent, and many patients have tumors that do not respond to the treatment, and scientists are trying to figure out why.
In addition, some immunotherapies, such as car-t and checkpoint inhibitors, are limited by T cell life. The cancer-fighting T cells in a tumor "run out" and die. So researchers are looking at ways to help t-cells used in immunotherapy last longer, and even encourage them to replicate and amplify.
The emergence of "potassium ions" offers hope. In the new study, Dr Nicholas Restifo found that t-cells grown in high-potassium environments also had "stem cell properties."
What's more, when researchers took these t-cells from tumor tissue and injected them into patients, the results showed that these "dry" t-cells could mature into killer t-cells in the body to fight cancer. T cells living in high concentrations of potassium were better able to shrink primary and metastatic melanoma in mice than those living in normal potassium.
The team confirmed that when they used specific drugs to mimic the effects of potassium on T cells, they also improved their ability to continue to grow and eliminate tumors. Dr Nicholas Restifo believes: "this research could help us better understand cancer immunotherapy and also provide clues to better and more lasting treatments."