Drug for metabolic disorders helps immune system to fight cancer

Sanquin researchers have found a way to induce a stronger immune response against cultured brain tumor cells. To this end, Robbert Spaapen and colleagues have removed certain lipids with a sugar headgroup, so-called glycolipids, from the outside of those tumor cells. They also exposed a molecular mechanism that controls the fabrication of those glycolipids. Intervention in this mechanism may improve the survival chances of patients. Spaapen already has a drug in mind. The research has been published in Immunity.

Our body cells are covered with many different kinds of glycolipids. Their functions are largely unknown. Robbert Spaapen and colleagues have discovered that a certain subtype of those can influence immune responses. These molecules obstruct recognition by the immune system. As a consequence, T cells (certain cells of the immune system) cannot properly kill the cells with these glycolipids.

Spaapen has discovered a new protein, SPPL3, that can stop the production of these glycolipids. This can be important for patients with the most common brain tumors, the gliomas. Several tumors have a lower amount of SPPL3, which leads to a higher production of the glycolipids. This group of patients has a worse chance of survival.

Pre-existing medicine
These patients may therefore benefit from inhibiting the glycolipid production. Spaapen envisions potential in a pre-existing drug, which is used to treat a very different type of diseases, namely certain hereditary metabolic diseases. This drug inhibits the formation of all glycolipids, and thus also the subtype that inhibits immune reactions. The researchers found that the drug indeed improves immune responses in the lab. It is therefore important to investigate in the coming years whether it will also work in patients.​