Researchers at the Indian Institute of Science (IISc), in a new study, have tried to understand how different types of cancer cells respond to Interferon-gamma (IFN-γ) activation.
According to IISc, cancer immunotherapy primes a patient’s immune system to better find and destroy cancer cells, improving upon the body’s natural ability to fight tumours.
“Contemporary immunotherapy approaches aim to stimulate immune cells called T cells to target tumours. In this process, the production and functioning of a cytokine (a small signalling protein) known as Interferon-gamma (IFN-γ) are essential for the immune system to eliminate tumours effectively. These approaches affect fewer normal cells when compared to chemotherapy or radiation. However, they are either very expensive or less efficient,” IISc said.
Only some respond
In the study they found that only some types of cancer cells respond well to IFN-γ activation, while others don’t. They also suggest some approaches that can be used to make these non-responsive cancer cells better respond to immunotherapy.
“IFN-γ is produced by immune cells such as T cells or natural killer cells. It binds to tumours, and induces apoptosis (cell death). Reports in the literature have shown earlier that if there are lower amounts of IFN-γ or defects in its signalling, then the tumours don’t respond well to the immunotherapy processes,” said Avik Chattopadhyay, first author and PhD student at the Department of Biochemistry, IISc.
In the current study, when the team first treated cancer cells in the lab with IFN-γ, they found that the colour of the cell growth medium changed to yellow, indicating that the cells were releasing acidic byproducts such as lactic acid. This led the team to dig deeper into the role of these byproducts. They found that the higher amounts of lactic acid produced in the cell culture medium was due to increased glycolysis, a series of chemical reactions that extracts energy from glucose.
Oxidative damage
The team found that cancer cell lines derived from the liver and the kidney showed increased production of nitric oxide (NO) and lactic acid upon IFN-γ activation. This, in turn, increased the production of toxic reactive oxygen species (ROS) leading to oxidative damage, which eventually kills the cancer cells.
However, cancer cell lines derived from the colon and skin did not produce NO or lactic acid even after being treated with IFN-γ, indicating that they might respond poorly to immunotherapy.
