This research will adapt techniques used to study how immune cells are activated against melanoma, a deadly cancer that quickly metastasizes to the brain, to the study of autoimmune brain disease, in which immune cells mistakenly target the brain.
These researchers have been studying how immune T cells, in an animal model of melanoma, can be activated by administering immunotherapies to reject melanoma tumors. A PET imaging technique used in the animal model allows them to follow the actions of the immune T cells throughout the body, including the brain, in pursuit of melanoma cells that have metastasized to the brain. The imaging technique has great sensitivity, enabling them to detect small numbers of immune T cells at any specific location in the body.
Now they will adapt this technique to explore how immune T cells become activated to attack the body’s own tissues in an animal model of the autoimmune disease multiple sclerosis (MS). In MS, immune T cells that are “autoreactive” somehow become activated in lymph tissues. They then mature and travel to the brain, mysteriously eluding the blood-brain-barrier, and attack the myelin sheath that insulates nerve fibers. This demeyelination process effectively disrupts cellular communication. By using this PET technique in the MS animal model, called EAE (experimental autoimmune encephalitis), and in the animal melanoma model, the research may identify common mechanisms of immune T cell activation and provide means for assessing the effects of immunotherapies on increasing T cell activation in melanoma and decreasing T cell activation in autoimmunity.
Significance: This research may enable the researchers to identify immune activation patterns that can serve as surrogate biomarkers for diagnosing autoimmune diseases and certain cancers affecting the brain,and for assessing the effects of immunotherapies used to treat them.