Doctor checking tube with blood analysis and making notes, lymphoma cancer
Researchers in Australia have identified a molecular “safety switch” that protects cancer cells from the immune system, thereby limiting the efficacy of current immunotherapy drugs for various cancers, including melanoma. This significant discovery, involving the TAK1 gene, was made by scientists at the Olivia Newton-John Cancer Research Institute and the Walter and Eliza Hall Institute in Melbourne. Their findings were published in the peer-reviewed journal Cell Reports on March 15, 2024.
The TAK1 gene enables cancer cells to evade attacks from the body’s killer T cells, which are crucial for fighting infections and cancers. In laboratory tests, researchers successfully utilized gene-editing technology to deactivate the TAK1 gene in cancer cells. This breakthrough could pave the way for more effective immunotherapy treatments that enhance the immune system’s ability to recognize and destroy cancerous cells.
According to Anne Huber, a postdoctoral researcher at OCJCRI and La Trobe University, the TAK1 gene serves as a central hub for various signaling pathways that manage essential bodily functions, including the immune response. Instead of being destroyed, cancer cells activate a survival pathway through the TAK1 gene, which produces “anti-death proteins.” This mechanism allows them to withstand immune attacks.
“It is known that TAK1 promotes cancer cell survival and blocks cell death; however, we didn’t know that cancer cells use this tactic to avoid being killed by the immune system,” Dr. Huber explained.
Potential for Improved Cancer Treatments
Current cancer immunotherapy approaches aim to enhance the immune system’s ability to detect and attack cancer cells. However, if tumors possess this “safety switch,” their effectiveness is significantly reduced. Conor Kearney, the lead researcher and head of molecular immunology at OCJCRI, stated that this research opens new avenues for cancer treatment.
“We aimed to understand why immunotherapy fails for many cancers, and we wanted our research to be unbiased,” Kearney noted. “We’ve shown we can combine drugs with existing immunotherapy to begin to target the protective protein.”
Researcher Tirta Djajawi emphasized that blocking TAK1 expression could considerably improve immunotherapy treatments. “If we remove the TAK1 gene, the tumor collapses under the force of the immune attack,” he said.
The study examined a variety of cancer types but focused primarily on melanoma, which is diagnosed in approximately 330,000 people worldwide annually. Melanoma is often treated with immunotherapy, and its incidence in Australia has risen from 53 cases per 100,000 in 2000 to an anticipated 70 cases per 100,000 in 2024, according to data from the Cancer Council. In 2020, melanoma was responsible for an estimated 1,340 deaths.
The research team will now investigate strategies to specifically target TAK1, with the aim of enhancing outcomes for cancer patients globally. By effectively disabling this safety switch, they hope to significantly advance the field of cancer immunotherapy.
