A revolutionary technique utilizing light to precisely target problematic cells for destruction has the potential to revolutionize our understanding and treatment of cancer and inflammatory diseases, according to researchers from the University of Illinois Urbana-Champaign.
Inflammatory cell death, known as necroptosis, is a vital mechanism the body employs to combat diseases. However, in certain conditions, such as cancer, cells can evade this process by suppressing inflammatory signals.
Traditional cancer treatments typically involve using drugs to induce cell death. Nonetheless, these drugs tend to spread throughout the body, leading to undesirable side effects. Professor Kai Zhang, the lead researcher, explains, “We have developed a method where cells can be activated by light, allowing us to focus the light precisely on a single cell, targeting its death pathway effectively.”
The researchers utilized a technique called optogenetics to make cells responsive to light. They integrated a light-sensitive gene from plants into intestinal cell cultures, alongside the gene for RIPK3, a protein that controls necroptosis.
Graduate student Teak-Jung Oh, the primary author of the study published in the Journal of Molecular Biology, elaborated, “Upon activation, RIPK3 forms protein clusters. By using light-sensitive proteins that cluster upon exposure to blue light, we can mimic the activation process.”
However, the objective is not merely to kill the cell itself. Triggering the inflammatory cell death pathway stimulates the immune system response. The ruptured cells release cytokines that attract T cells, key players in identifying and combating threats in the immune system.
Zhang commented, “Certain cancer cells establish an immunosuppressive environment, hindering T cell response. By inducing necroptosis in cancer cells, we aim to alter this immune-suppressed state, enhancing T cell recognition and attack on cancerous cells.”
While the optogenetic system currently limits human clinical applications to tissues near the skin due to the need for direct light delivery, the research team plans to advance their system to mouse models for further exploration of necroptosis and immune response in cancer and inflammatory diseases.
Oh remarked, “Understanding the signaling pathway for necroptosis is crucial for diseases like neurodegenerative and inflammatory bowel diseases. Identifying these molecular mechanisms is essential for developing targeted therapies to halt disease progression.”
Funding for this study was provided by the National Institute of General Medical Sciences, National Institute of Mental Health, National Science Foundation, and the Cancer Center at Illinois. Zhang is also associated with the Beckman Institute for Advanced Science and Technology at Illinois. The National Institutes of Health supported this work through grants R01GM132438 and R01MH124827.
