Tel Aviv University Scientists Discover Game-changing Cancer Therapy Pathway

Researchers discuss the groundbreaking discovery of a unique protein linked to immune suppression, while the potential of finding new treatments for cancer inspires one of the scientists throughout his military service

Researchers at Tel Aviv University have made a significant breakthrough in cancer treatment, discovering a mechanism that could help eliminate tumors, even those resistant to current immunotherapy. The research, published in Nature Communications, was led by Prof. Carmit Levy, Prof. Yaron Carmi, and PhD student Avishai Maliah from the Faculty of Medical and Health Sciences.

While most cancer research focuses on how tumors themselves inhibit the immune system, the team at TAU took a different approach. Combining expertise in cancer biology and immunology, they identified a previously overlooked protein, Ly6a, that plays a crucial role in immune suppression in other contexts. In laboratory animals, it appears that blocking this protein helps shrink even the most stubborn tumors.

Immunotherapy has revolutionized cancer treatment, (but) about 50% of people never respond to the drugs. So, we need to come up with new strategies.

Prof. Carmit Levy told The Media Line that a primary question in cancer biology is how a cancer manages to escape the immune system. The immune system may recognize that something is wrong in a specific area of the body but cannot combat the cancer cells effectively. “Immunotherapy has revolutionized cancer treatment,” she said, but “about 50% of people never respond to the drugs. So, we need to come up with new strategies.”

“When the immune system identifies cancer and approaches to attack,” Levy explained, “the cancer cells express inhibitory molecules that act as brakes, blocking the immune system from activating fully. The immune cells might be there, but they’re unable to kill the tumor cells because of these molecules.” Research worldwide is focused on uncovering these molecules and understanding how they communicate with and suppress immune cells.

Her novel approach emerged when Levy asked herself, “What natural systems in our body are designed to suppress the immune system? That’s when I thought about UV radiation. Phototherapy, for instance, is used to treat autoimmune skin conditions like psoriasis by inhibiting immune activity. It’s an external cue that essentially tells the immune system to calm down.”

This insight led her lab to investigate whether tumors might use a similar mechanism. “Instead of starting with tumor data, we examined how UV exposure affects immune suppression. We found that after UV exposure, there was a significant increase in a protein called Ly6a,” Levy recounted. “We checked it in tumors, and there it was—Ly6a was highly upregulated. It felt like a bingo moment.” This protein was blocking the immune system’s effort to eliminate the tumor.

The team then tested this discovery. “We used antibodies to block Ly6a, and the results were remarkable. Tumors that didn’t respond to PD1 immunotherapy in mice responded when treated with the Ly6a antibody. The immune system began to eliminate the tumors,” she said, calling it “an incredibly unique route and discovery.”

We are searching for the human version of this protein to see if it behaves the same way. If so, we’ll have something significant to say for human treatments.

Levy also discussed the ongoing efforts to transition from animal models to human applications. “For the past two years, we’ve been working on translating our findings to humans,” she stated. “We are searching for the human version of this protein to see if it behaves the same way. If so, we’ll have something significant to say for human treatments. In our mouse model, it worked for both melanoma and colon cancer, and we hope that in humans, it could be effective against various types of cancer.”

When asked about the timeline for developing a human drug, Levy replied, “If we had an unlimited budget, it could be done in two years, but realistically, we might be looking at five to ten years.” She acknowledged the financial challenges in scientific research. “Budget is always an issue. We’re constantly writing grants and proposals. But we’ve been fortunate to receive prestigious support from organizations like the ERC and have collaborations worldwide, from Germany and France to the US,” she said.

Science is a global effort, with no borders. We collaborate because our interest is in science and nothing else.

Collaboration is central to her work, and Levy spoke with pride about her team. “Science is a global effort, with no borders. We collaborate because our interest is in science and nothing else,” she shared. She praised the contributions of PhD student Avishai Maliah, who led the project despite recently returning from military duty in Lebanon, and Prof. Yaron Carmi, whose expertise in immunology was crucial. “Without their support, this would never have happened,” she said.

Science requires a puzzle-like collaboration. You need experts in different fields, and when everything comes together, it creates something amazing. That’s the magic of science.

Reflecting on the project, Levy concluded, “Science requires a puzzle-like collaboration. You need experts in different fields, and when everything comes together, it creates something amazing. That’s the magic of science.”

PhD student Avishai Maliah told The Media Line that what he finds most captivating about his research is the potential for a new form of cancer immunotherapy.

“I think the most interesting point is that we’ve uncovered a different way to approach immunotherapy,” he said. “Immunotherapy is now recognized as one of the best methods to fight cancer, but there are only a few options that provide a full cure, and most operate with similar mechanisms. Our discovery of Ly6a is exciting because it represents a completely different pathway. It’s based on modulating T-cells in a unique way, which could be a game-changer for patients who haven’t responded to existing treatments.”

Maliah described the results of his PhD work: “Our findings showed that UV primarily affects the skin, with specific impacts on T-cells and other cells there. Once we understood how UV influenced immune suppression, we asked whether the molecule Ly6a we had identified was also active in cancer. We found that even without UV exposure, Ly6a played a major role in suppressing T-cells in tumors. That was a pivotal discovery, showing us that this molecule could be targeted to improve immune response against cancer.”

Maliah also spoke about his concurrent military service. “One week ago, I was in Lebanon. Balancing everything is not easy. I’ve been studying for a medical degree and a PhD, which means constant juggling among studying, research, and military service. I completed my PhD a year ago, but I’m still in medical school with exams coming up this week. So, I come home from service, and then I’m back to my research or preparing for exams. It’s a lot, but surprisingly, I’ve found ways to stay focused.”

“Even in Lebanon,” Maliah continued, “I kept up with my studies and thought about research. Not all research needs to be done in a lab or at a specific place. Our brains can solve problems or come up with ideas anywhere, even in a war zone. It’s almost comforting, knowing that I have something important waiting for me when I return.”

Maliah added that having a clear sense of purpose drives him forward. “It’s challenging, yes, but I think it’s also rewarding. Knowing that I’m working on something that could one day help cancer patients gives me a sense of accomplishment and hope. And honestly, it helps me handle the stress of everything else.”