Researchers have identified the reason behind cancer's resistance to immunotherapy, shedding light on its inefficacy.

A recent study conducted by the University of Alabama at Birmingham has revealed a new method to enhance cancer immunotherapy by overcoming resistance to drugs known as immune checkpoint blockers (ICB). These treatments assist the immune system in attacking cancer, but they often fail when tumor-fighting T-cells cannot operate in low-oxygen environments. This issue, referred to as hypoxia, is commonly found in tumors, as reported by Drug Target Review.

The research, led by Dr. Lewis Zhichang Shi and published in the journal Nature Communications, explains how HIF1α supports T-cells in producing a crucial immune molecule called interferon gamma (IFN-γ), which is essential for destroying cancer cells. HIF1α also aids T-cells in generating energy through a process known as glycolysis, which becomes vital under low oxygen conditions.

Without HIF1α, T-cells are unable to combat cancer in hypoxic tumors, significantly reducing the effectiveness of ICB therapy. To test their theories, the researchers utilized specialized mouse models and experimental treatment methods. They discovered that when HIF1α was removed, T-cells could not switch to the energy-producing glycolytic pathway, leading to a decline in their ability to attack tumors. Conversely, stabilizing HIF1α helped restore these cells' capacity to fight cancer, even in challenging conditions.

The addition of a compound called acetate allowed the scientists to bypass the need for HIF1α altogether, enabling T-cells to regain their strength and attack tumors more effectively in conjunction with ICB. This discovery could lead to significant advancements in the treatment of various types of cancer that are currently resistant to multiple therapies. By targeting the HIF1α pathway, researchers hope to develop strategies to enhance the immune system's response to cancer, even in patients who previously did not respond to ICB therapy.

This approach may help overcome one of the biggest obstacles in immunotherapy—treatment resistance caused by the harsh tumor environment. Combinations such as enhancing glycolysis or adding acetate could greatly increase the success of cancer treatments in the future, the authors believe.

Important! This article is based on the latest scientific and medical research and does not contradict it. The text is for informational purposes only and does not contain medical advice. For a diagnosis, please consult a physician.