MELBOURNE, Dec. 20 (Xinhua) -- Scientists in Australia have identified a molecular "safety switch" that helps cancer cells evade immune attack, revealing a mechanism for tumors to resist immunotherapy treatments.
Researchers discovered that the TAK1 gene acts like the safety switch that protects cancer cells from the powerful signals generated by CD8+ T cells, key killer cells of our immune system, a media release from Australia's Olivia Newton-John Cancer Research Institute (ONJCRI) said Saturday.
TAK1 was identified by conducting a large genetic screen to search for genes that help cancer cells survive attacks by CD8+ T cells, according to ONJCRI, which led the research in collaboration with Australia's Walter and Eliza Hall Institute of Medical Research.
"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 killing by the immune system," said Anne Huber, postdoctoral researcher at ONJCRI.
When TAK1 was blocked in laboratory models using CRISPR gene-editing, tumors grew poorly, demonstrating that the immune system is able to control cancer cells better, according to the study published in Cell Reports.
"Without TAK1, the cancer cells lose a key protein, cFLIP, that normally prevents cell death, and they become far more sensitive to immune attack," Huber said, adding that turning off TAK1 makes cancer cells much easier for the immune system to eliminate, offering hope for more powerful treatment options.
Tirta Djajawi, a postdoctoral researcher at ONJCRI, said blocking TAK1 could make current immunotherapies more effective "by stripping tumors of this protection."
"TAK1 is like a shock absorber that lets cancer cells survive the immune system's hardest hits. Remove it, and the tumor collapses under the force of immune attack," Djajawi said.
Cancer immunotherapies can work very well, but underperform in some cases due to tumors' inbuilt survival processes that help them resist attack by the immune system.
The research was conducted across a variety of cancer types, predominantly melanoma, which is often treated with immunotherapy. ■