Unwanted side effects associated with pharmacological induction may soon be avoided when targeting troublesome cells for inflammatory cell death.

Researchers at the University of Illinois Urbana-Champaign have developed a method to precisely target cells for inflammatory cell death using light, which could lead to new treatments for cancer and inflammatory diseases. 

In the study featured in the Journal of Molecular Biology, the researchers used optogenetics, inserting a light-activated gene into intestinal cell cultures. This gene attaches to the gene for the necroptosis-regulating protein RIPK3, activating cell death pathways.

"When activated, RIPK3 undergoes oligomerization — it forms clusters of protein complexes. Our light-sensitive proteins cluster together when exposed to blue light. So by triggering the light-sensitive proteins to come together, the RIPK3 comes together and oligomerizes, and that's how we mimic the activation pathway," explained Teak-Jung Oh, the paper's first author. 

This process then triggers an immune response as the ruptured cells release cytokines. These cytokines irritate nearby cells and attract T cells to the affected area.

"Certain cancer cell types create a local immunosuppressive environment, where T cells are either not recruited or, if they do come, they do not recognize it as a threat and do not infiltrate the cancerous area. But by opening up some cancer cells through necroptosis, we hope to modulate this immune suppressive environment and help train the T cells to recognize and attack the cancer," said Kai Zhang, a biochemistry professor at the University of Illinois and the study's leader.

While human clinical applications are currently limited, further studies using mice to study necroptosis and immune response in cancer and other inflammatory diseases are planned. The team also intends to explore the method's potential in immunotherapy. 

Included in the team are David Shapiro, a biochemistry professor at the University of Illinois, and Junyao Zhu, a graduate student.

Read the full article here to learn more about optogenetics.

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