Israeli researchers identify protein that stops immune cells from attacking tumors

[Micael]

This sounds a bit promising. If we can eventually get to the point where we can treat effectively cancer without chemo and radiation, avoiding the damaging effects of those, the upside would be massive.

Israeli researchers identify protein that stops immune cells from attacking tumors

Tel Aviv University team finds Ly6a protein 'puts the brake' on the immune system, in discovery that points to a cure for cancers, including those resistant to immunotherapy

By Diana Bletter
Israeli researchers identify protein that stops immune cells from attacking tumors
For the first time, researchers at Tel Aviv University say they have identified a protein that prevents the body’s immune system from attacking tumors.

The discovery of the protein has enabled the scientists to modify its activity, allowing them to stimulate the immune system to fight cancer cells.

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The breakthrough could lead to new treatments for cancer, including types that are resistant to immunotherapy.

“We found a protein mechanism that puts a brake on the immune system, and we were able to remove it so that the immune system worked again,” said Prof. Carmit Levy, who co-authored the study with Prof. Yaron Carmi and PhD student Avishai Maliah, all of TAU, and other researchers in Israel and Massachusetts.

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“This is an exciting discovery,” Levy told The Times of Israel.

The study was published in September in Nature Communications.

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Israeli researchers identify protein that stops immune cells from attacking tumors
Illustration of T-cells attacking a cancer cell (royalty stock photo via iStock by Getty Images)
Here comes the sun

The breakthrough occurred by coincidence, Levy said. As a cancer biologist, she usually studies cancer and the effects of UV radiation — or sunlight — on the skin.

In a healthy immune system, she explained, the body knows when there’s a virus inside it and works efficiently to counter it. But in an autoimmune skin disease like psoriasis, the immune system sees the body’s own skin cells as harmful and triggers a response against them.

Doctors use ultraviolet light therapy, known as phototherapy, to help treat psoriasis by “putting a brake” on the immune system so that it stops overworking.

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Levy said that she and Maliah made the connection between one system — phototherapy — and another, cancer.

“Phototherapy lessens the immune system’s over-activation,” Levy said. “Cancer cells also inhibit the immune system so it doesn’t work properly, making it under-act.”

Sunlight is far different from cancer, she said, yet both have a distinct impact on the functioning of the immune system.

“Let’s say you know that running makes you tired and reading makes you tired,” Levy said. “These are two very different activities, but both make you tired. What are the markers they share?”

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Israeli researchers identify protein that stops immune cells from attacking tumors
The sun sets over the Mediterranean Sea near Ashkelon on September 12, 2014. (AP/Tsafrir Abayov)
On the hunt for a protein

In 2020, Levy and Maliah joined forces with Carmi, an immunologist, to proceed with their research.

“After the initial discovery, we wanted to go deeper into the immunology field, so we all started investigating together,” Levy said.

To understand the process of how an immune cell can fight a cancer cell, Levy suggested thinking about it like a Hollywood movie.

“You can imagine that the immune cell is coming, ready to kill the cancer cell,” Levy said. “But a tumor cell stops the immune cell, so it’s just standing there without the ability to kill. The cancer cells keep growing.”

In the first part of their experiment, the scientists observed the effect of UV exposure on various proteins.

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The team discovered a significant increase in one specific protein, Ly6a. Little was known about this protein’s role in the immune system’s ability to recognize and fight cancer cells.

Levy said that after the skin was exposed to UV radiation, immune cells called T cells — a key to fighting cancer — began producing high levels of the Ly6a protein. The protein was “telling the immune cells to slow down,” she said.

The role of the protein was positive when it came to an autoimmune disease. But with cancer, the protein played a negative role. The team suspected that Ly6a might be sending signals to the immune system’s T cells to stop attacking tumors.

After they discovered Ly6a’s possible impact on immune cells, Carmi called Levy one night at 11 p.m. “He was so excited and told me, ‘I’ve never seen something like this in my whole career,'” she said.

Testing the hypothesis

To test whether Ly6a protein might be the cause of the immune system’s slowdown, the scientists treated it with an antibody.

Without its presence, “the brakes were released,” Levy said. “The immune system was free to attack the cancer cells.”

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The tumors were significantly reduced. Moreover, she said, even cancers that usually didn’t respond to treatment began shrinking.

Israeli researchers identify protein that stops immune cells from attacking tumors
Tel Aviv University PhD student Avishai Maliah found Ly6a protein with Prof. Carmit Levy and Prof. Yaron Carmi. (Nerya Maliah)
Hope for cancer treatment

The researchers discovered an uptick of Ly6a protein in melanoma skin cancer and colon cancer, Levy said, and they “have reason to suspect that it exists in other cancers as well.”

However, the Ly6a gene was found only in mice. It doesn’t exist in humans, but “there might be another gene that comes close that we will be able to use,” she said.

Levy believes that scientists will be able to find the right gene, she said. “As in life,” she joked, “we just need to find the right guy.”

The scientists began working on human genes two years ago, hoping to develop their findings into a drug that could become a new cancer treatment for people. She said the process could take another five to 10 years.

“We are highly motivated to find a solution,” Levy said. “We have some hints, and that brings hope.”

[Rocket J Squrriel]

The glioblastoma multiforme brain tumor is hard to treat because there are only a couple chemo drugs that can touch it. Even then with radiation and surgery cells are left behind and the tumor grows back. A few people can live for years with treatment cycles but most pass fairly quickly. The hospital, docs, nurses, and tech gave my Beloved and I tend wonderful months.

An interesting treatment that is being studied is hit it with the Zika virus. That was one that made the new several years ago because if pregnant women got it, it made them miscarry or have the baby born with birth defects. They also noticed that the virus LOVES to kill glioblastoma cells and not healthy, normal cells. It can also stimulate the natural defense to go after glios too. They're looking at the why it has this hate, how it works, and can it the targeting/kill function be tamed so its not an infectious disease. Oh and if you're healthy, not pregnant you might not notice you have/had Zika.