Researchers at the University of Bern have discovered a mechanism in the body’s own immune system that is responsible for the maturation and activation of immune cells.
In the fight against skin cancer, the results have the potential to help immunotherapies succeed, even in patients for whom they have so far been ineffective.
Melanoma is a malignant tumor of pigment cells. If diagnosed early, the tumor can be completely removed, and the chances of recovery are good. But in later stages, when the tumor has already spread or metastasized elsewhere in the body, the outlook is worse for those affected.
There is no effect for half of the patients
So-called immune checkpoint inhibitors, which have been approved for the past ten years, are a ray of hope – and the medical profession has achieved spectacular successes in treating these drugs. However, in a good half of patients these therapies do not show any beneficial effect. But now, the work of the research group led by Miriam Schenk from the Institute of Pathology at the University of Bern shows a promising way to increase the effectiveness of treatment and help many more patients than before.
In collaboration with US researchers, Schenk’s team has discovered the role of a signal molecule that cells of the body’s immune system use to coordinate their functions. The molecule is called Interleukin-32, IL-32 for short. In the complex interaction of immune cells within and in the immediate area around a tumor, he soon revealed a double effect. “Hit two birds with one stone,” says Schenk.
Making tumors attackable again
On the one hand, IL-32 leads to the maturation and activation of so-called dendritic cells that are responsible for the recognition of foreign structures. In addition, IL-32 also causes macrophages or scavenger cells to secrete attractants for T cells. This is how these immune cells find their way to the tumor, where they can kill cancer cells.
Tumors have to escape detection by the immune system in order for them to grow. That is why they are installed in immunosuppressed environments that are hospitable to cancer growth. Clearly, IL-32 is able to make these tumor protective niches again accessible to the immune system. With trials in mice, the researchers led by Schenk have shown that the efficacy of immune checkpoint inhibitors can be enhanced by simultaneous administration of IL-32.
Combination therapy is a “promising therapeutic strategy.”
In animal models, the additionally administered IL-32 did not cause any side effects. It remains to be seen if these results can be transferred to humans, Schenk says. Yet another argument certainly speaks in favor of the fact that combination therapy represents a “promising strategy for treatment,” as the researchers led by Schenk write in their recently published article in the “Journal of Clinical Investigation insight.” As they have been able to demonstrate with bioinformatic analyzes, melanoma patients with higher IL-32 activity have a longer life expectancy, from a statistical point of view