Light-Activated Immune Response

Optogenetics has been a popular tool for studying and controlling nerve pathways, but now an international team of researchers reports using optogenetic techniques to “instruct” immune cells to kill cancerous tumors (eLife, doi: 10.7554/eLife.10024). Using a mouse model of melanoma, the team used its optogenetic platform—called Opto-CRAC, after the immune-response regulating Ca²⁺ release-activated Ca²⁺ (CRAC) channel in the cell membrane—to trigger a site- and cancer cell-specific immune response in T lymphocytes, macrophages and dendritic cells.

Immunotherapy is a popular area in cancer research because it aims at killing cancer cells using the body’s own cells, which can be more effective and less harmful than traditional, more toxic treatments like chemotherapy and radiation. But optogenetic immunomodulation has a major problem: Immune cells are located deep within the body, which makes them hard to “activate” with the blue light used in optogenetics. To overcome this problem, the scientists designed a platform that uses near-infrared (NIR) laser light, which can penetrate a centimeter or two below the skin’s surface, and upconversion nanoparticles that act as nanotransducers to convert NIR light into the blue light needed to activate the optogenetically engineered immune cells.

Led by Texas A&M (USA) assistant professor Yubin Zhou, the researchers tested Opto-CRAC using mouse melanoma models. The study mice were injected with upconversion nanoparticles and immune cells with optogenetically modified CRAC channels. When they shined an NIR laser light at the mice, the blue light produced by the nanoparticles triggered the light-sensitive immune cells to open their Ca²⁺ channels. (In vitro studies showed that increasing the intensity of the blue light caused even more calcium ions to cross into the cell membrane.) The influx of Ca²⁺caused the immune cells to “activate” and kill the melanoma cells. And when the NIR light was turned off, the Ca²⁺ channels closed and the immune response stopped.

Results from their tests with the mouse tumor models showed a reduction in tumor size and metastasis. Zhou says: “Other scientists will likely use the technique to help them study immune, heart and other types of cells that use calcium to perform their tasks.”