The Indian Institute of Science (IISc) conducted research on enhancing immunotherapy in cancer cells that did not respond to treatment.
An innovative finding by scientists at the Indian Institute of Science (IISc) may greatly enhance the efficacy of cancer immunotherapy, a medical intervention that uses the immune system to fight cancer cells.
The study explores the complex function of interferon-gamma (IFN-γ), a cytokine essential for immune response, and its interactions with different cancer cells. It was just published in Frontiers in Immunology.
For patients, cancer immunotherapy has been a ray of hope since it provides a more focused approach than conventional treatments like radiation or chemotherapy, which frequently cause damage to healthy cells. The expense and inconsistent effectiveness of various treatments have presented difficulties, though.
In Depth
The study conducted by the IISc team sought to resolve these problems by examining the many ways in which cancer cells react when IFN-γ is activated.
The study’s first author, PhD candidate Avik Chattopadhyay of IISc’s Department of Biochemistry, says that IFN-γ is secreted by T cells or natural killer cells and can trigger apoptosis in tumour cells. However, the cancer cells might not react well to immunotherapy if IFN-γ or its signalling pathway is lacking.
In multicellular organisms, apoptosis—also known as programmed cell death—is a tightly controlled and regulated process.
The cell growth medium turned yellow when the researchers treated cancer cells with IFN-γ, indicating the release of lactic acid and an acidic environment. They investigated the metabolic mechanisms underlying this phenomena as a result of this observation.
They found that when triggered by IFN-γ, cell lines from liver and kidney cancer increased the amount of nitric oxide (NO) and lactic acid they produced. This led to the creation of harmful reactive oxygen species (ROS), which have the potential to kill cells.
Skin and colon cancer cell lines, on the other hand, did not show the same reaction, which may indicate immunotherapy resistance.
In order to overcome this, the group tried a number of techniques to cause these resistant cells to produce lactic acid and NO. Amazingly, adding potassium lactate changed everything by drastically slowing the growth of even the cancer cells that were unresponsive.
Conclusion
Given that lactic acid is generally seen as a metabolic waste product, this discovery was surprising.
The study is currently essentially a proof-of-concept, according to the corresponding author, Professor Dipankar Nandi.
Especially for tumours that are challenging to treat, he underlines the need for more study in animal models to ascertain if focusing on metabolic pathways can augment the anti-tumour effects of IFN-γ during immunotherapy.
