Domestic researchers have discovered a substance that interferes with immunotherapy for lung cancer. Immunotherapy harnesses our body's immune cells to attack cancer cells and has gained attention for its advantages of fewer side effects. It is expected that identifying substances that diminish the effectiveness of such immunotherapy will lead to enhanced cancer treatment outcomes.
The Korea Advanced Institute of Science and Technology (KAIST) announced on the 8th that a research team led by Professor Kwon-hyun Cho from the Department of Bio and Brain Engineering discovered 'DDX54,' a key factor that hinders immunotherapy.
Immunotherapy uses the immune cells in the body as a treatment method. The problem is that fewer than 1 in 5 patients respond to immunotherapy. Various studies are underway to treat patients who do not respond to immunotherapy.
Typically, tumor mutation burden (TMB) is used as an indicator to select patients who respond to immunotherapy. The more genetic mutations there are, the higher the likelihood of responding to immunotherapy. However, it is known that lung cancer does not respond adequately to immunotherapy, even when there are many genetic mutations, because the immune cells cannot penetrate lung cancer cells effectively.
The research team inferred the genetic regulatory network through transcriptomics and genetic data derived from lung cancer patients. This led to the discovery of DDX54, which hinders immunotherapy in lung cancer. The team inhibited DDX54 in a mouse model with lung cancer and confirmed that this increased the response to immunotherapy. Additionally, T cells that suppress cancer were promoted, while regulatory T cells that aid cancer cell growth were inhibited.
The researchers are transferring this technology to BioRevert, a faculty startup, to develop it as an immunotherapy combination treatment. Clinical trials are set to begin in 2028. The results of this study were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on the 2nd.
Professor Kwon-hyun Cho noted, "By discovering (DDX54) and controlling it, we are able to develop a new treatment strategy that can induce responses in cancers that previously did not respond to immunotherapy."
References
PNAS (2025), DOI: https://doi.org/10.1073/pnas.2412310122