Proteomic Mapping Links Lipid Metabolism to Failed Immunotherapy

Researchers at the Tel Aviv University and Sheba Medical Center at the Tel HaShomer Hospital have found why the immunotherapy cancer treatments fail to treat patients with metastatic melanoma through proteomic mapping.

The researchers were investigating why melanoma patients had a positive response to immunotherapy while metastatic melanoma did not. A team found the answer under the guidance of Prof. Tami Geiger, Prof. Gal Markel, and Dr. Michal Harel.

Prof. Markel serves as an oncologist and director at the Ella Lemelbaum Institute. Prof. Geiger heads the TAU’s Proteomics Lab.

The team members were from the TAU’s Sackler School of Medicine and Sheba’s Ella Lemelbaum Institute for Immuno-Oncology employed Wielding proteomics as the tool to dig deep into cell composition.

The findings of the study appear in the journal Cell. During the study, the doctors supervised 116 patients of melanoma. Researchers also analyzed the responses of melanoma patients to immunotherapy.

The results did not bear fruit under the first test. This was because immunotherapy failed in one group of patients but was successful in a bunch of others. Researchers used proteomic mapping to find the proteins which were playing a role at the cellular level.

The team discovered key differences in the way the cells worked. Also, the cells had contrasting metabolism in the cancer cells of the two groups.

Failed Immunotherapy Response

Prior to this research, researchers have made many attempts in cancer immunotherapies to strengthen the immune system against cancer. The treatments revolutionized oncology.

The scope of the research was why many patients do not respond to immunotherapy.

The recent research targeted metastatic melanoma which had no treatments until recently. Firstly, the researchers took the pre-treatment specimens from the patients who responded to immunotherapy and from those who did not.

The disease itself is deadly and causes over 7000 deaths annually. Then to develop a better understanding they examined the specimens from 116 patients using proteomic mapping. This helped to understand the treatment resistance mechanism within the tumors.

A mass-spectrometer assisted in mapping the various proteins involved. As the number of proteins was in thousands, an extensive computational analysis was also used to identify the proteins that set the two groups apart.

The proteomic comparison proved very fruitful. It successfully identified major differences that separated responders from non-responders.

Those who responded to immunotherapy had higher levels of proteins associated with lipid metabolism. This led to better recognition by the immune system.

Clinical Trials: Blocking Lipid Metabolism

The team collaborated with the Salk Institute in San Diego and Yale School of Medicine to further examine the findings.

Researchers used a mouse model of metastatic melanoma to examine the melanoma tissue cultures. Genetic engineering was used to halt the underlying process of fatty acid metabolism.

On blocking the metabolic pathway for the fatty acid metabolism, the troublesome cancer cells are shielded from T-cells that are responsible to detect and destroy them.

This was quite disastrous as cancer in these mice developed at a much faster pace as compared to the control group.

The findings are relevant not just for Metastatic melanoma but for most if not all cancerous growths. The study successfully pinpointed the contrasting factors between the different melanoma patients.

While some lived on for years aided by immunotherapy others were not so fortunate. Research on the subject has paved the way for this to change.

Further studies are being carried out to enhance the response of the immune system to immunotherapy. This includes enabling doctors to form an informed opinion as to whether a patient would respond to immunotherapy or not.

The study has helped in mapping and pinpointing the proteins involved in the process of lipid metabolism. Its role in shielding the cancerous growths from the T-cells was analyzed for the first time and will help in saving millions of lives.

Adeena Tariq

Adeena's professional life has been mostly in hospital management, while studying international business in college. Of course, she now covers topics for us in health.

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