Study May Lead to Safer Immunotherapy for Mesothelioma

New research conducted in Europe and at Harvard University may open the door to safer immunotherapy for mesothelioma patients. 

Immunotherapy is one of the most promising approaches to fight malignant mesothelioma. But the potential side effects can be devastating. 

Now, new data suggests there are ways to reduce the complications of immunotherapy for mesothelioma. The key is to target some of the white blood cells that trigger inflammation. Inflammation is the driver behind most of the serious side effects of immunotherapy. 

Why Harness the Immune System?

No one ever expects to contract mesothelioma. It is an extremely rare cancer. Most people who get it have spent time living or working around asbestos. Even among asbestos-exposed people, mesothelioma is rare. Scientists suspect that there is a certain amount of genetic susceptibility involved.

For people unfortunate enough to contract mesothelioma, the prognosis is not good. Treatments that work for other kinds of cancer do not work well for mesothelioma. 

In recent years, researchers have doubled down on their efforts to develop effective immunotherapy for mesothelioma. Immunotherapy attacks cancer from the inside out. It turns the patient’s own immune system against their mesothelioma tumor. 

Several new immunotherapy drugs have produced hopeful results in some mesothelioma patients. But some patients develop complications that are so serious they have to stop treatment. In these cases, immunotherapy for mesothelioma works against healthy cells as well as cancer cells. 

“When the immune system is activated so intensively, the resulting inflammatory reaction can have harmful effects and sometimes cause significant damage to healthy tissue,” says Mikaël Pittet of the Swiss Cancer Centre Leman, a cancer research consortium.

If doctors can find a way to confine the effects to mesothelioma cells, it could mean safer, more effective immunotherapy.

A New Understanding of Toxicity in Immunotherapy for Mesothelioma

The new research comes from the University of Geneva in Switzerland and Harvard Medical School. Scientists figured out the difference between a cancer-fighting immune response and a damaging immune reaction. 

Researchers studied biopsy samples from liver cancer patients. The patients had toxic reactions to immunotherapy. According to the University of Geneva, “while the immune mechanisms are similar, the cell populations involved are different.” The study sheds light on toxic reactions to immunotherapy for mesothelioma and other cancers, too.

The researchers say macrophages and neutrophils are involved in the inflammatory response that harms healthy tissue. Another type of cells called dendritic cells trigger the inflammation that destroys cancer cells. 

This understanding may help scientists create more targeted therapies that “turn on” dendritic cells without activating macrophages and neutrophils. 

“Inhibiting neutrophils could be a more effective way to fight cancer: in addition to triggering a toxic response, some of these cells also promote tumor growth,” writes Dr. Pittet. “Thus, by managing to control them, we could have a double beneficial effect: overcome the toxicity in healthy tissues, and limit the growth of cancerous cells.” 

Last year, the FDA approved a combination of Opdivo and Yervoy as immunotherapy for mesothelioma. Other immunotherapy drugs are still being tested. 

Source: 

Siwicki, M, et al, “Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy”, July 2, 2021, Science Immunology, Volume 6, Issue 61, https://immunology.sciencemag.org/content/6/61/eabi7083.full