Protein Mapping Pinpoints Why Most Metastatic Melanoma Patients Do Not Respond to Immunotherapy

Written on |

Lipid metabolism found to affect cancer cells’ visibility to the immune system, say TAU, Sheba Medical Center researchers

Tel Aviv University and Sheba Medical Center researchers say they have discovered why more than half of patients with metastatic melanoma do not respond to immunotherapy cancer treatments.

Wielding proteomics, an innovative “protein mapping” approach, a team of researchers led by Prof. Tami Geiger, Prof. Gal Markel, and Dr. Michal Harel of TAU’s Sackler School of Medicine and Sheba’s Ella Lemelbaum Institute for Immuno-Oncology have answered the burning question: Why do immunotherapy treatments greatly help some patients with melanoma but not affect 60 percent of metastatic melanoma patients?

The researchers, whose findings were published on September 5 in Cell, compared the responses of 116 melanoma patients to immunotherapy — one group in which immunotherapy was successful and a second in which immunotherapy was not successful. Harnessing proteomics, a powerful protein mapping technology, they discovered differences in the metabolism, or energy production process, of the cancer cells of the two groups.

“In recent years, a variety of cancer immunotherapy therapies have been used, therapies that strengthen the anti-cancer activity of the immune system,” explains Prof. Markel, a senior oncologist and scientific director of the Ella Lemelbaum Institute. “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.

“Can we predict who will respond? Can we alter treatment in order to increase responses? In our research, we focused on metastatic melanoma, a devastating disease that until recently had no efficient treatments. It was clear to us that pre-treatment samples from responders and non-responders would be key.”

To better understand treatment resistance mechanisms, the scientists examined tumors taken from 116 patients using proteomics.

“In the proteomic lab, we use an instrument called a mass-spectrometer, which enables global mapping of thousands of proteins,” explains Prof. Geiger, head of TAU’s Proteomics Lab. “We then followed up with extensive computational analysis to identify the proteins that differentiated between the response groups.”

The proteomic comparison identified major differences between responders and non-responders to immunotherapy. “In the responders, we found higher levels of proteins associated with lipid metabolism, which led to better recognition by the immune system,” says Prof. Geiger.

In collaboration with the Salk Institute in San Diego and Yale School of Medicine, researchers then examined their findings in melanoma tissue cultures and a mouse model of metastatic melanoma.

Using genetic engineering, they were able to silence the mechanism responsible for fatty acid metabolism.

“We found that upon silencing this metabolic pathway, the cancer cells manage to ‘hide’ from T-cells that are supposed to detect and destroy them,” says Prof. Geiger. “As a result, cancer in these mice developed at a faster rate compared to the control group.

“In our study, we identified a significant difference between melanoma patients who live for years thanks to immunotherapy, and patients who are not at all affected by the treatment.”

“These findings can also be relevant to many other malignancies,” adds Prof. Markel. “Now, in subsequent studies, we are looking for ways to improve the response to immunotherapy and expand the circle of patients who benefit from it. In addition, we are looking for a method that will allow clinicians to anticipate which patients will respond to treatments.”

related posts

Recruiting ‘Fighting Cells’ to Destroy Tumors

September 14, 2021

TAU Team Reverses Early Signs of Alzheimer’s

September 10, 2021

Nicotine Testing of Children Curbs Parents’ Smoking

September 5, 2021

The Silent Prophets

August 31, 2021

Want to Fall in Love? Step Outside in The Sun

August 30, 2021

First 3D-bioprinting of entire active tumor

August 18, 2021

New Warning Sign for Breast Cancer

August 6, 2021

COVID-19 Immunity Varies Among Genders and Age Groups

July 25, 2021

New study found differences between women and men in the level of COVID-19 antibodies

July 15, 2021

A world first: Technology that restores the sense of touch in nerves damaged as a result of amputation or injury

July 15, 2021

New nanotech from TAU produces “healthy” electric current from the human body itself

July 9, 2021

Want to Live a Long Life? Consider Investing in Your Marriage.

July 2, 2021

A world first: Targeted delivery of therapeutic RNAs only to cancer cells, with no harm caused to healthy cells

June 30, 2021

Combating Antibiotic Resistance

June 22, 2021

Diamonds in the Rough

June 3, 2021

How Will We Brave the Post-COVID Era?

May 31, 2021

Are We Getting to the Root of Cancer?

May 3, 2021

Optical Technology Generates Immediate Melanoma Diagnosis

April 27, 2021

Gut Healing

April 25, 2021

Could Your Smartphone Be Damaging Your Teeth?

April 4, 2021

The Quest for A Lifesaving Cure

March 16, 2021

A Healthier Alternative to Antibiotics

February 24, 2021

Children with Autism during Lockdown: Serious Implications for Behavior and Development

February 22, 2021

Cancer Breakthrough: Cells’ Uniqueness is Also Weakness

January 29, 2021

TAU Scientists Develop Innovative Therapy to Prevent Deafness

December 28, 2020

Two TAU Professors Win 2020 Nature Mentoring Award

December 28, 2020

Lack of Teacher Support during Pandemic Causes Acute Emotional Harm

December 4, 2020

New Discovery: Development of the Inner Ear in Embryos is Similar to Crystal Formation

November 26, 2020

In First, Aging Stopped in Humans: TAU Co-Study

November 23, 2020

TAU developed genome editing system destroys cancer cells

November 20, 2020

TAU Co-Study: “Green Revolution” Decreased Infant Mortality

November 17, 2020

Study: Women Suffer More from COVID-related Orofacial Pain

November 12, 2020

Global First: Center for Combating Pandemics

October 22, 2020

TAU Researchers Discover Antibody Combo that Fights COVID-19

October 12, 2020

Researchers Identified the Genetic Causes of Inherited Hearing Loss in the Jewish Population of Israel

September 30, 2020

Targeting Melanoma

September 9, 2020

TAU Inaugurates Shmunis School of Biomedicine and Cancer Research

September 8, 2020

Physical exercise can help improve both physical and mental health

August 31, 2020

New school for Biomedicine and Cancer Research at Tel Aviv University

August 13, 2020

An Experimental Drug for Alzheimer’s May Help Children with Autism

August 5, 2020

TAU Study: Stimulating Immune System Prevents Post-Surgery Metastasis

July 27, 2020

TAU Researcher Fights Epidemics Both Viral and Virtual

July 23, 2020

TAU study: Oxygen therapy improves cognitive function in seniors

July 16, 2020

TAU-led Team Destroys Cancer Cells with Ultrasound

July 9, 2020

New nanomedicines for mRNA therapeutics in breast cancer and heart failure

July 6, 2020

3D printed heart used to test life-saving drugs

June 29, 2020

Did climate change cause infections 6,000 years ago?

May 21, 2020

Accurate 3D imaging could significantly improve IVF treatments

May 18, 2020

TAU study finds widespread misinterpretation of gene expression data

December 26, 2019

Fibroblasts involved in healing spur tumor growth in cancer

December 23, 2019
Ontario and Western Canada

3130 Bathurst Street, Suite, 214, Toronto, ON | M6A 2A1 
Phone: 416.787.9930 | Toll Free: 833.32.CFTAU (22328)
Email: toronto@cftau.ca

Ottawa, Quebec and Atlantic Canada

6900 Boulevard Décarie, Suite 3480, Montreal, QC | H3X 2T8
Phone: 514.344.3417
Email: montreal@cftau.ca


© CFTAU  | all rights reserved
Charitable registration: 124035643RR0001

TO TOP