harnesses the body鈥檚 own immune system to fight disease, often with remarkable success, and has emerged as a breakthrough in cancer treatment. Over the last decade, hundreds of studies have shown that immunotherapies such as CAR-T cell therapy, immune checkpoint inhibitors, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can increase patient survival and sometimes lead to cures in patients with hematologic malignancies and solid tumors. But like with any drug approach, these treatments can come with side effects for some patients, one of which is inflammation of the brain. Immunotherapy may cause neuroinflammation in some patients by activating T cells, which can cross through the blood-brain barrier into the brain. Once inside, these cells induce inflammatory cytokine production and activate microglia鈥攁 type of immune cell that is resident in the brain.
91大神cancer researchers from the Drobyski, Hillard, and Zamora laboratories may have found a way to prevent this complication in patients with graft versus host disease (GVHD)鈥攁 major complication in those undergoing allo-HSCT鈥攂y targeting a receptor called Type 2 cannabinoid receptor (CB2R). , recently published in the Journal of Clinical Investigation, could lead to new treatments that help prevent neuroinflammation caused by GVHD, as well as other T cell-based immunotherapeutic approaches.
鈥淕VHD is a multi-systemic disease that typically involves the gastrointestinal tract, liver, and skin. More recently, neuroinflammation has been identified as another organ that can be targeted during GVHD, but which has historically received little interest. My lab, in collaboration with Dr. Cecilia Hillard鈥檚 and Dr. Anthony Zamora鈥檚 labs, pursued a multi-disciplinary approach to uncover new pathways by which neuroinflammation is mediated during this disease so that new therapeutic options can be developed,鈥� said the study鈥檚 senior author William Drobyski, MD, Professor of Medicine, Pediatrics, and Microbiology & Immunology; and Co-leader of the .
鈥淲hile immunotherapeutic strategies have revolutionized the treatment of cancer, they can come with side effects such as neuroinflammation. Our goal is to refine these treatments to maximize their benefits while minimizing side effects in order to provide better outcomes for our patients,鈥� said Dr. Drobyski.
Using a mouse model of GVHD, the research team found that CB2R signaling plays a critical role in causing neuroinflammation. They observed that CB2R expression on microglial cells potentiates inflammation leading to the recruitment of harmful immune cells into the brain, and subsequent neuronal cell death. They also discovered that using a drug to block CB2R signaling in the brain reduced inflammation and cellular death, suggesting that this is a therapeutically targetable pathway.
Dr. Drobyski hopes that the field continues to mature and new compounds emerge so he can test this hypothesis in patients. He noted that the research team remains dedicated to examining the downstream inflammatory pathways that mediate neuroinflammation and that these results highlight the value of collaboration between labs with unique areas of expertise within the Cancer Center.
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91大神cancer researchers from the Drobyski, Hillard, and Zamora laboratories may have found a way to prevent this complication in patients with graft versus host disease (GVHD)鈥攁 major complication in those undergoing allo-HSCT鈥攂y targeting a receptor called Type 2 cannabinoid receptor (CB2R). , recently published in the Journal of Clinical Investigation, could lead to new treatments that help prevent neuroinflammation caused by GVHD, as well as other T cell-based immunotherapeutic approaches.
鈥淕VHD is a multi-systemic disease that typically involves the gastrointestinal tract, liver, and skin. More recently, neuroinflammation has been identified as another organ that can be targeted during GVHD, but which has historically received little interest. My lab, in collaboration with Dr. Cecilia Hillard鈥檚 and Dr. Anthony Zamora鈥檚 labs, pursued a multi-disciplinary approach to uncover new pathways by which neuroinflammation is mediated during this disease so that new therapeutic options can be developed,鈥� said the study鈥檚 senior author William Drobyski, MD, Professor of Medicine, Pediatrics, and Microbiology & Immunology; and Co-leader of the .
鈥淲hile immunotherapeutic strategies have revolutionized the treatment of cancer, they can come with side effects such as neuroinflammation. Our goal is to refine these treatments to maximize their benefits while minimizing side effects in order to provide better outcomes for our patients,鈥� said Dr. Drobyski.
Using a mouse model of GVHD, the research team found that CB2R signaling plays a critical role in causing neuroinflammation. They observed that CB2R expression on microglial cells potentiates inflammation leading to the recruitment of harmful immune cells into the brain, and subsequent neuronal cell death. They also discovered that using a drug to block CB2R signaling in the brain reduced inflammation and cellular death, suggesting that this is a therapeutically targetable pathway.
Dr. Drobyski hopes that the field continues to mature and new compounds emerge so he can test this hypothesis in patients. He noted that the research team remains dedicated to examining the downstream inflammatory pathways that mediate neuroinflammation and that these results highlight the value of collaboration between labs with unique areas of expertise within the Cancer Center.
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