07/10/2024
Well-known immunotherapy target also plays role in diminishing immune response
New Cleveland Clinic research shows that activating the STING protein to fight cancer could inadvertently shut off our body’s defenses, leading to a net negative. The findings, published in PNAS, can guide academia and industry to improve immunotherapy treatments.
Activating STING during immunotherapy is an attractive method for drug developers to try and improve low treatment responses. The protein STING is well known for its contribution to our innate immune system, the body’s first line of defense. The protein helps patrol our systems and induce inflammation in response to invading pathogens and tumor cells. However, further research into the protein and its use in immunotherapy revealed STING also plays a role in reducing immune response.
“Immunotherapy that activates STING has shown great promise in multiple preclinical studies but has encountered problems in clinical trials and nobody knows know why,” says senior author Jianjun Wu, PhD, who recently received $2.3 million from the National Institutes of Health to study the protein. “Our findings provide a plausible answer: the protein also activates T-cell repressors, which dampen immune function and promote tumor growth.”
Dr. Wu leads a laboratory in the Center for Immunotherapy and Precision Immuno-Oncology. His team collaborated with Xianfang Wu, PhD, to map out the signaling pathways that STING uses to activate T-cell repressors. The investigators plan to further investigate how the protein balances its immune-activating and dampening activities.
“If we can figure out the conditions that promote STING’s pro- and anti- immune effects, we can also replicate them during immunotherapy,” says Dr. Jianjun Wu. “In doing so, we hope to improve treatment outcomes and patient quality of life.”
Dr. Xianfang Wu, whose laboratory is in Infection Biology, adds that STING’s anti-immune effects have therapeutic potential beyond cancer treatments.
“Dampening the immune response through STING could be a promising therapeutic strategy for autoimmune diseases like systemic lupus erythematosus or rheumatoid arthritis,” he says. “That’s why it’s important that we don’t take a protein’s functions for granted: further research can always show us new possibilities.”
