Israeli Researchers Discover Why Some Melanoma Patients Don’t Respond to Immunotherapy Treatments

Sheba Medical Center, Tel HaShomer and Tel Aviv University researchers have uncovered why 60% of patients suffering from a deadly form of skin cancer, metastatic melanoma, don’t respond to immunotherapy treatments. This discovery is critical because it can help oncologists choose the best treatment options and potentially work on ways to make more patients receptive to life saving immunotherapies.

Researchers at Sheba Medical Center, Tel HaShomer and Tel Aviv University (TAU) have discovered why 60% of patients with metastatic melanoma – skin cancer that has spread to other parts of the body – do not respond to immunotherapy. Immunotherapy treatments use the body’s own immune system to control and eradicate cancer.

Melanoma is the most dangerous type of skin cancer. More than 7,000 people will die from melanoma this year in the United States.

The study was conducted by a team of researchers led by Prof. Tami Geiger, Dr. Michal Harel and Prof. Gal Markel of TAU’s Sackler School of Medicine and Sheba’s Ella Lemelbaum Institute for Immuno-Oncology.

“In recent years, a variety of cancer immunotherapy therapies have been used, therapies that strengthen the anti-cancer activity of the immune system,” explained Prof. Gal Markel, a senior oncologist and scientific director of the Ella Lemelbaum Institute at Sheba Medical Center, Tel HaShomer.

“These treatments have been shown to be highly effective for some patients and have revolutionized oncology. However, many patients do not respond to immunotherapy, and it is critical to understand why,” added Markel.”

The scientists examined tumors taken from 116 patients using proteomics. In this new approach, also called “protein mapping,” researchers mapped thousands of proteins. They found differences in the metabolism, or energy production process, of the cancer cells in patients who responded to immunotherapy and those who did not.

In the study published in Cell earlier this month, researchers reported that the non-responding patients tended to have lower fatty acid metabolism, meaning that their enzymes broke down fat for energy at a slower rate.

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“In our study, we identified a significant difference between melanoma patients who live years thanks to immunotherapy, and patients who are not at all affected by the treatment,” said Prof. Geiger, head of Tel Aviv University’s Proteomics Lab.

Due to these findings, oncologists now know to check the levels of fatty acid metabolism in their melanoma patients and advise those who have high levels to pursue immunotherapy. Researchers say it may also be possible to raise the levels of fatty acid metabolism in cancer cells with medication to make more patients receptive to immunotherapies. A follow-up study will focus on that area.

Sheba’s Prof Gal Markel is available for interviews on this key discovery and how it could change the treatment options for melanoma patients.

About Sheba Medical Center, Tel HaShomer 
Born together with Israel in 1948, Sheba Medical Center, Tel HaShomer is the largest and most comprehensive medical center in the Middle East. Sheba is the only medical center in Israel that combines an acute care hospital and a rehabilitation hospital on one campus, and it is at the forefront of medical treatments, patient care, research and education. As a university teaching hospital affiliated with the Sackler School of Medicine at Tel-Aviv University, it welcomes people from all over the world indiscriminately. In 2019, Newsweek magazine named Sheba one of the top ten hospitals in the world. To learn more, visit: eng.sheba.co.il

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These treatments have been shown to be highly effective for some patients and have revolutionized oncology. However, many patients do not respond to immunotherapy, and it is critical to understand why.