Some Melanoma Patients Don't Respond to Immunotherapy

New Proteomics Research Reveals Why Some Melanoma Patients Don’t Respond to Immunotherapy

Approximately 60% of patients with metastatic melanoma, a type of skin cancer that has spread to other organs, do not exhibit a response to life-saving immunotherapy treatments. Recent research has uncovered the reason, which was published in Cell earlier this month.

The studies were jointly conducted by scientists from Sheba’s Ella Lemelbaum Institute for Immuno-Oncology and Tel Aviv University’s (TAU) Sackler School of Medicine. Prof. Tami Geiger, Dr. Michal Harel, and Prof. Gal Markel led the team of researchers.

Immunotherapy makes use of the body’s own immune system to control and eliminate cancer cells. This type of treatment has been extremely effective in treating some patients with melanoma, the most dangerous type of skin cancer.

“In recent years, a variety of cancer immunotherapies 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.

To conduct their seminal research, the scientists inspected tumors extracted from 116 patients. By performing proteomics (“protein mapping”), they mapped thousands of proteins and discovered meaningful differences in the metabolism of cancer cells in patients who reacted to immunotherapy versus those who did not. In the non-responsive patients, enzymes break down fat for energy at a slower pace, so they had a lower fatty acid metabolism.

“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.

These findings provide an effective way to determine the best candidates for immunotherapy treatment. When designing personalized treatments for their melanoma patients, oncologists can now check their fatty acid metabolism levels. Additionally, researchers claim it may be possible to give medication to increase the cancer cells’ levels of fatty acid metabolism in order to make patients more receptive to immunotherapy. A follow-up study aims to investigate and pursue this approach.