New Light-Activated Technique Targets Cancer and Inflammatory Cells with Precision

Researchers at the University of Illinois Urbana-Champaign have developed a new method to precisely target and kill problematic cells using light. This breakthrough could lead to better treatments for cancer and inflammatory diseases.

Inflammatory cell death, known as necroptosis, is a crucial process the body uses to fight diseases. However, in some cases, this process can malfunction. For instance, cancer cells can block inflammatory signals, allowing them to avoid death.

Traditional cancer treatments often use drugs to kill cells, but these chemicals can spread throughout the body, causing unwanted side effects. “We can make cells sensitive to light and use a focused light beam smaller than a single cell to target and activate their death pathway,” explained Kai Zhang, the study leader and a biochemistry professor at the University of Illinois.

The researchers employed a technique called optogenetics to make cells respond to light. They took a light-activated gene from plants and inserted it into intestinal cell cultures, linking it to the gene for RIPK3, a protein that controls necroptosis.

“When RIPK3 is activated, it forms clusters of protein complexes. Our light-sensitive proteins also cluster together when exposed to blue light. By triggering these proteins with light, we can make RIPK3 cluster and activate the cell death pathway,” said Teak-Jung Oh, a graduate student and the first author of the paper published in the Journal of Molecular Biology.

The goal isn’t just to kill the cell. Inducing the inflammatory cell death pathway triggers the immune system to respond. The dying cells release chemicals called cytokines, which irritate nearby cells and attract T cells. T cells are white blood cells that help the immune system identify and attack threats, Zhang explained.

“Some cancer cells create an environment that suppresses the immune system, preventing T cells from recognizing and attacking them. By causing necroptosis in some cancer cells, we hope to change this environment and help T cells recognize and attack the cancer,” said Zhang, who is also a member of the Cancer Center at Illinois.

Currently, this optogenetic system requires direct light delivery to tissues, limiting its use in human tissues deeper than the skin. However, the Illinois team plans to test their system in mice to further study necroptosis and immune responses in cancer and other inflammatory diseases. They also aim to explore the potential of this platform for training T cells for immune therapies.

“Understanding the cell signaling pathway for necroptosis is crucial because it is involved in diseases like neurodegenerative diseases and inflammatory bowel disease. Knowing how necroptosis affects these diseases is important. Without understanding the molecular mechanisms, it’s hard to know what to target to slow disease progression,” Oh said.

This research was supported by the National Institute of General Medical Sciences, the National Institute of Mental Health, the National Science Foundation, and the Cancer Center at Illinois. Zhang is also affiliated with the Beckman Institute for Advanced Science and Technology at Illinois.