A possible therapeutic strategy to treat viral infection and increase immunity against cancer is reported in the online May 30 issue of the journal. Cell.
The work, conducted by scientists at the Wake Forest School of Medicine, found that increasing production of type 1 interferon in the body helped eliminate viral infection and increased immunity to cancer by identifying a sensor involved in the suppression of cancer. the production of interferon in an animal model.
Interferons are a group of signaling proteins created and released by host cells in response to the presence of several viruses. In a typical scenario, a cell infected with the virus will release interferons, which will cause nearby cells to increase their antiviral defenses.
Interferons also help the immune system fight cancer and can slow the growth of cancer cells.
The study's principal investigator was Hui-Kuan Lin, Ph.D., professor of cancer biology at Wake Forest School of Medicine, part of Wake Forest Baptist Health.
In the study, Lin's team discovered that RIG-I-like receptors (RLRs) mediated the production of interferon (IFN), which played a critical role in raising host immunity for viral clearance and surveillance immunological of cancer. They reported that glycolysis, the first step to break down glucose to extract energy for cell metabolism, was inactivated during RLR activity. This inactivation served as the key to activate IFN type I production.
Using pharmacological and genetic approaches, the scientists demonstrated that reducing lactate by inactivating lactate dehydrogenase A (LDHA) increased the production of type I IFN to protect it from viral infection in mice.
The study established a critical role of lactate derived from glycolysis in limiting RLR signaling and identified MAVS as a direct lactate sensor, which works to connect energy metabolism and innate immunity, Lin said.
Type I interferons (IFNs), produced by almost every cell type, played a vital role in the defense of the host against viral infection and immunosurveillance of cancer, said Lin.
Lin's team plans to conduct additional studies on other animal models in preparation for possible clinical trials.
This work was supported by Start-ups and The Endowment Fund of the Anderson Discovery Professor for Cancer Research at the Wake Forest School of Medicine; The National Institutes of Health (NIH) grant R01CA182424 and R01CA193813; and NIH grants R01CA194094 and R01CA197178. The research team also recognizes the support of the National Key Research and Development Program 2017YFA0503900, the National Natural Science Foundation of China 31671413 and the Beijing Nova Program Z161100004916147; and Main Program of the National Science Foundation of China 81790252.
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Materials provided by Wake Forest Baptist Medical Center. Note: The content can be edited by style and length.