Scientists identify cancer mechanism that could transform immunotherapy
Israeli researchers uncovered a groundbreaking mechanism in cancer treatment that could potentially eradicate tumours resistant to current immunotherapies.
Tel Aviv University on Aug. 20, 2024. Photo by Yossi Zeliger/TPS-IL
Scientists from Tel Aviv University identified a previously unknown cancer mechanism that prevents the immune system from attacking tumours effectively. In an unexpected twist, they found that by reversing this mechanism, the immune system is stimulated to attack and eliminate cancer cells.
Their research, led by Professor Carmit Levy, Professor Yaron Carmi, and MD/PhD candidate Avishai Maliah, was recently published in the peer-reviewed Nature Communications journal.
The breakthrough came about by chance, as Professor Levy’s lab is dedicated to studying both cancer and the impact of ultraviolet (UV) radiation on the immune system. UV exposure is known to suppress immune activity in the skin
“Cancer and UV radiation both suppress the immune system, but the mechanism was unclear. While most researchers focus directly on cancer mechanisms, we took a different approach by examining how UV radiation affects immune suppression in the skin,” Levy explained. This unique approach led to the unexpected discovery of a protein that plays a pivotal role in immune suppression.
The team then embarked on an extensive study of immune system changes triggered by UV exposure. Using a mouse model, Maliah examined the behaviours of various proteins in response to UV exposure and observed a notable increase in a protein called Ly6a—a relatively under-researched protein. This discovery marked the beginning of a pivotal understanding of Ly6a’s role in immune suppression and its potential applications in cancer therapy.
As the researchers continued their investigations, they uncovered that Ly6a functions as a brake on the immune system, specifically affecting T cells that play a crucial role in combating cancer.
“After exposure to UV radiation, we noticed that T cells began expressing high levels of Ly6a, which seemed to inhibit the immune response,” explained Maliah. “Our hypothesis was that by releasing this brake, we could restore optimal immune activation.”
Further study revealed that Ly6a is not only present in UV-exposed skin cells but also overexpressed in certain cancerous tumours. According to Levy, they found heightened Ly6a levels in melanoma and colon cancer cells, suggesting a broader mechanism by which cancer cells deactivate the immune system.
“We were able to observe that this protein desensitizes immune T cells in multiple cancers. By treating tumors with Ly6a antibodies, we saw a significant reduction in tumor size,” Levy explained.
The discovery of Ly6a could have significant implications in the field of immunotherapy, an area of cancer treatment that has made substantial progress over the last decade by harnessing the body’s immune system to combat cancer. However, approximately half of all patients fail to respond to widely used PD1-based therapies, which often have side effects on the immune system.
“We found that antibodies targeting Ly6a eradicated tumors in our animal models, even in cases where tumors were resistant to PD1 therapy,” Carmi said. “This opens the door to developing an entirely new class of drugs targeting Ly6a, potentially helping a significant portion of patients who do not respond to existing immunotherapies.”
The researchers stress that further study is needed to translate these findings into a clinical setting. Current efforts are focused on developing a drug based on these findings to test its efficacy and safety in human trials. If developed into a viable drug, this discovery could lead to an entirely new class of treatments to better harness the immune system’s power.
“Cancer treatment has made huge strides with immunotherapy, but gaps remain. With our discovery, we are working toward closing these gaps and offering a new, effective treatment for patients worldwide,” said Carmi.
