Scientists at the VIB-UGent Center for Medical Biotechnology have taken important steps forward in the development of a cancer-targeting immunotherapy. The research team developed a treatment in mice that destroys part of the tumor and stimulates the immune system to attack persistent surviving cancer cells. In addition, the researchers demonstrated that the treatment provides protection against the development of tumor formation in other areas of the body. Their findings have been published in Nature Communications.

Chemo- and radiotherapy are effective in reducing tumor size, but they unfortunately also affect healthy cells. The human immune system is a more accurate weapon, which has evolved to recognize and eliminate disease-causing cells. However, cancer cells employ a range of different strategies to confuse and thwart the immune system. Immunotherapies, which help stimulate the immune system to better identify specific cancer cells, show promising results, but are still in need of a great deal of improvement.

An example for the immune system

The team of Prof. Xavier Saelens (VIB-UGent Center for Medical Biotechnology) seeks to enhance immunotherapy approaches in an inventive way by provoking a certain type of cell death, called necroptosis, in cancer cells. Previous VIB research has demonstrated that when cells die from necroptosis, the immune system is alarmed.

PhD student Lien Van Hoecke (VIB-UGent Center for Medical Biotechnology): "This phenomenon is also called immunogenic cell death, as the dying cells become examples for the immune system, which then learns and remembers which cells to search for and attack."

Dual effect

Building on that knowledge, the team went looking for a way to provoke necroptosis in cancer cells and thus 'teach' the immune system how to attack tumors. The researchers explored MLKL, a protein that plays a crucial role in necroptosis, for their research goal.

Lien Van Hoecke (VIB-UGent Center for Medical Biotechnology): "We developed an immune therapy that causes part of the cancer cells to produce MLKL. As a result, these cancer cells die. The dead cells then activate the immune system, which attacks tumor cells that survived the initial treatment."

Prof. Xavier Saelens (VIB-UGent Center for Medical Biotechnology): "Our treatment not only inhibits primary tumor growth in mice, but also provides protection against untreated tumors and disseminated tumors. This is because the immune system is able to recognize cancer cells located in other areas of the body after confronting destroyed cells in the treated tumor. The outcomes of our study open up a number of avenues for the application of this therapy in humans."