A new American study has shown that a specific type of fat called “sphingolipids” is necessary for cancer to escape the immune system, to the point that some cancer cells cannot reproduce without it.
The results confirmed long-standing suspicions that this type of fat is not only a key player in cancer biology (and therefore an important target for cancer-fighting drugs), but also showed that existing FDA-approved drugs designed to reduce fat production could boost the immune system against cancer.
Cancer cells announce their presence to the immune system by sticking out chemical “red flags” on their membranes, and rarely start hiding. At the heart of this early warning system are fats, fatty compounds that cancer scientists previously viewed primarily as fuel for growing tumors. Once alerted, the body’s defenses can step in and destroy cancer cells before they can do too much damage.
“We thought that high levels of fat were a source of energy for cancer cells,” says Kivanc Birsoy, the study’s lead researcher at the Laboratory of Metabolic Regulation and Genetics at Rockefeller University in the United States. “We discovered that it is a more complex mechanism, where fat acts as a protective mechanism for cancer cells that modifies how they communicate with the immune system.”
The mysterious relationship between fat and cancer
Scientists have long known that cancer cells alter fat metabolism, but it has generally been assumed that these cancer cells consume these fats for energy, using the fat molecules to help the tumor grow and spread more than healthy cells.
“We knew from scientific research that high levels of fat are linked to the severity of cancer growth and spread, but it was not clear how this happens,” researcher Marelis Sola, a former graduate student in Kivanc Birsoy’s lab, said, according to EurekAlert.
The researchers set out to answer this question by examining the genes involved in this process. They then implanted a series of cancer cells, each lacking a specific gene, into mice with both healthy and damaged immune systems, revealing that the cancer cells could not survive without sphingolipids. The results of the study were published in the journal Nature on August 7.
Sphingolipids are a type of lipid discovered in the late 19th century by the German chemist Johann Ludwig Wilhelm Thudekum, and named after the Sphinx in Greek mythology because of their mysterious structure and function. Two centuries later, these lipids are less mysterious. “We now know that sphingolipids are not really used for energy,” says Sola. “They are mainly found in the cell membrane, providing scaffolding for signaling proteins.”
Towards a new treatment strategy
To test how sphingolipids stimulate cancer growth, the team turned to an FDA-approved drug used to treat Gaucher disease, a genetic disorder marked by the inability to break down fats. The team found that the drug inhibited tumor growth in models of pancreatic, lung, and colorectal cancer.
They also found that reducing sphingolipids prevents the formation of “lipid nanodomains” that bind signaling molecules together on the membrane, affecting cell surface receptors and making them more sensitive to immune response.
These findings suggest that cancer cells store sphingolipids to mask inflammatory signals, and that disrupting production of this substance could make cancer cells vulnerable to immune attack.
It also suggests that pharmacological and nutritional interventions that block sphingolipid production may help increase the effectiveness of current immunotherapies.