IRAK3 protein affects response to cancer immunotherapy


A recent study by IGP researchers shows that the protein IRAK3 reduces the effect of immunotherapy against cancer. One way of improving the therapy response could be to reduce the amount the IRAK3 with drugs that target the protein.  

Immunotherapy has become an increasingly effective way to treat cancer but in some cases the therapy has little or no effect. This can be because myeloid cells, a type immune cell, are recruited to the tumour where they inhibit the antitumour effect of the immune response.

In the present study, the researchers found that the myeloid cells’ influence on immunotherapy is controlled by the protein IRAK3.

“IRAK3 was discovered some 20 years ago but it is only until only now we have determined its role as an ‘immunological brake’ in myeloid cells. One could say that IRAK3 induces signalling pathways in the myeloid cells that in turn inhibits the immune response in other kinds of immune cells,” says Yumeng Mao, who led the study.

The researchers used different strategies to investigate the role of IRAK3. For instance, they created mice that did not produce any IRAK3 protein. When they studied tumours in these mice, they found a delayed tumour growth and prolonged survival.

“We also studied how mice without IRAK3 responded to immunotherapy. For one tumour type, which is normally not responsive to immunotherapy, we found reduced tumours in mice lacking IRAK3 after immunotherapy. For another tumour type, we did not find tumours at all in most mice lacking IRAK3 after immunotherapy. These results show that IRAK3 has an important role for the effect of immunotherapy,” says Yumeng Mao.

In another part of the study, the researchers analysed data from a large immunotherapy clinical trial. They examined the amount of IRAK3 mRNA in urothelial cancer patients before immunotherapy and found that patients who had lower IRAK3 levels before the treatment responded better and showed an improved survival.

“It was very exciting to see such a strong predictive effect on the response to immunotherapy in patients with advanced cancer. This means that our results have an implication in patients. By targeting IRAK3 the outcome of immunotherapy could be improved. There are new drugs against IRAK3 entering clinical trials soon and hopefully this will help improve response rates in cancer patients,” says Marta Rúbies Bedós, one of the study’s first authors.

The study has been published in Journal of Clinical Investigation.

More information:

Article in Journal of Clinical Investigation

Yumeng Mao’s research

Last modified: 2022-01-26