TAK1 Molecular Switch Could Strengthen Cancer Immunotherapy

Scientists are seeking to improve cancer treatment by helping the body’s own immune system fight the disease more effectively. A new study has identified a molecular switch that may offer a way to do this.

TAK1 helps cancer cells evade the immune system

Using a large-scale screening method, researchers switched off genes in laboratory-grown cancer cells to identify their effects. They found that the gene responsible for producing the TAK1 protein was essential in enabling cancer cells to escape immune attack.

Additional experiments in mice with functioning immune systems confirmed TAK1’s importance to cancer progression. Tumours lacking this protein grew at a slower rate, while the mice lived longer on average.

The team, which included researchers from institutions in Australia and Ireland, believes the results could support the creation of future treatments. Drugs might be able to target TAK1 production directly and ‘flip’ this molecular switch.

“It is known that TAK1 promotes cancer cell survival and blocks cell death,” says cancer cell biologist Anne Huber, from the Olivia Newton-John Cancer Research Institute (ONJCRI) in Australia.

“However, we didn't know that cancer cells use this tactic to avoid killing by the immune system.”

How TAK1 protects tumours from CD8⁺ T cells

Huber and her colleagues investigated the processes behind TAK1’s effects in more depth. In particular, the protein shields cancer cells from CD8⁺ T cells, immune cells that remove damaged cells and destroy dangerous invaders such as cancer cells.

CD8⁺ T cells work partly by releasing chemical signals known as cytokines. When TAK1 is absent, these signals can reach their targets more easily.

A detailed understanding of this mechanism may help scientists use it more effectively in cancer treatments. Without TAK1, cancer cells are effectively attempting to survive without one of their strongest protectors.

Potential for future immunotherapy treatment

It is important to note that the research used cancer cells grown in the laboratory and tumours in mouse models. Although there is reason to think the findings may translate to humans, this still needs to be investigated across a wider variety of cancers; the study focused mainly on melanoma.

Even so, the findings are promising. A key advantage of immunotherapy approaches for tackling tumours is that they rely more heavily on the body’s natural defences than on chemotherapy medicines or radiation.

Patient safety remains a vital consideration for every cancer treatment.

Preventing TAK1 production could become possible in future, but researchers will need to establish any harmful effects elsewhere in the body and balance these against the potential benefits.

“Blocking TAK1 could make current immunotherapies more effective by stripping tumors of this protection,” says medical biologist Tirta Djajawi, from ONJCRI.

“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.”

The research was published in Cell Reports.