BENGALURU: Scientists at the IISc have discovered new ways that can help make non-responsive cancer cells better respond to immunotherapy.
The study also found that not all cancer cells respond the same way to contemporary immunotherapy that aims to stimulate immune cells called T cells to target tumours, which was published in Frontiers in Immunology.
In immunotherapy, the production and functioning of a cytokine (a small signalling protein) known as Interferon-gamma (IFN-^) are essential for the immune system to eliminate tumours. In the study, researchers tried to understand how different types of cancer cells respond to IFN-^ activation and found that only some types of cells respond well to the protein activation, while some don’t.
“IFN-^ is produced by immune cells such as T cells or natural killer cells. It binds to tumours, and induces apoptosis [cell death],” said Avik Chattopadhyay, first author and PhD student at the Department of Biochemistry, IISc. He added: “Reports in the literature have shown earlier that if there are lower amounts of IFN-^ or defects in its signalling, then the tumours don’t respond well to the immunotherapy processes.” Immunotherapy affect fewer normal cells when compared to chemotherapy or radiation. However, they are either very expensive or less efficient.
Meanwhile, to improve their outcome, the scientists treated cancer cells in the lab with IFN-^ and found that the colour of the cell growth medium changed to yellow, indicating that the cells were releasing lactic acid. This was due to the increased glycolysis, a series of chemical reactions that extracts energy from glucose.
Researchers found that cancer cell lines derived from the liver and kidney showed increased production of nitric oxide (NO) and lactic acid upon IFN-^ activation. This increases the production of toxic reactive oxygen species (ROS) leading to oxidative damage, which kills the cancer cells. “However, cancer cell lines from the colon and skin did not produce NO or lactic acid even after being treated with IFN-^,” stated the release.