An Italian study, directed and coordinated by Humanitas, funded by AIRC and published in Nature, has unveiled the anticancer role of IL-1R8, the new immunity brake involved in tumor development. IL-1R8 has demonstrated the action of mediator of resistance against tumors and metastases in human defense cells, particularly in the liver and lung, blocking their development.

In a service by TGR Leonardo, Professor Alberto Mantovani, Scientific Director of Humanitas and Dr. Cecilia Garlanda, Head of the Laboratory of Experimental Immunopathology in Humanitas, spoke about this topic.

In the presence of a tumor, part of the immune system “passes to the enemy”, thus holding back our immune response. IL-1R8 is one of these brakes, capable of inhibiting the activity of NK cells, a specialized group of immune cells capable of killing cancer cells. The gene was identified in 1998 by the team of Professor Mantovani and recently, the research has made an important step forward, thanks to this new study.


The discovery and the research

“We have discovered that if we remove this molecule – which we had identified several years ago – we give a license to kill NK cells; these cells, for example in the liver, mediate resistance to liver cancer and above all eliminate metastases to the liver and lungs. To have demonstrated that we can remove this brake in human cells was an important first step, now we have to demonstrate in a pre-clinical context that it can work, and that it can also do so together with the weapons we already have: the path we have ahead is long,” explained Professor Mantovani.

“Mostly we worked with in vitro cells where we could genetically inactivate this molecule and then study the biological activity of the cells in which the molecule had been eliminated,” said Dr. Garlanda.


Future scenarios

This discovery now travels on two tracks: the diagnostic track, using the IL-1R8 molecule as a marker of immune system activity, and the therapeutic track, with tools that block this brake to release anticancer cell activity. The therapies today are already able to counteract two brakes (PD-1 and CTLA4) and antibodies are used to inhibit them.

“To remove these two brakes in the clinical field, we have faced a twenty-year path, i.e. twenty years have passed from discovery to translation for the benefit of the patient. We will do everything we can to save time,” said Professor Mantovani.