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The discovery reveals how the cancer sends out microscopic vesicles that bind to and immobilize the very lymphocytes designed to destroy tumors.
By Shula Rosen
Israeli researchers say they have identified a mechanism that allows melanoma to disable the body’s defenses, a finding Tel Aviv University believes could lead to new forms of immunotherapy.
The discovery reveals how the cancer sends out microscopic vesicles that bind to and immobilize the very lymphocytes designed to destroy tumors.
The study, published in Cell, was led by Prof. Carmit Levy of Tel Aviv University’s Department of Human Genetics and Biochemistry and involved teams from Israel, the United States, and Europe, including Sheba Medical Center, the Weizmann Institute of Science, the Technion, Hadassah Medical Center, Massachusetts General Hospital, Paris-Saclay University, and the University of Zurich.
Researchers said the process begins when melanoma cells produce large numbers of extracellular vesicles, or EVs—tiny packets previously linked to the cancer’s ability to spread.
The new work shows that these vesicles also carry a specific ligand that binds receptors found only on tumor-killing lymphocytes.
Prof. Levy said she first noticed the molecule while examining the vesicle membrane. “I noticed that on the vesicle membrane there was a molecule—a ligand—that binds to a receptor found only on certain immune cells called lymphocytes,” she explained to The Jerusalem Post. Initial lab work, she said, suggested these vesicles were effectively freezing immune cells in place. “It was an unusual idea, but the lab experiments confirmed it.”
The findings prompted an international collaboration to test the hypothesis using patient-derived samples. According to Levy, the collective work demonstrated that the cancer “essentially fires these vesicles at the immune cells, stopping them from working and sometimes even killing them.”
Melanoma is the deadliest form of skin cancer, causing an estimated 57,000 deaths a year and accounting for roughly 325,000 new diagnoses annually worldwide. The disease begins in pigment-producing cells and can rapidly move from the outer skin layer to deeper tissue and into the bloodstream and lymphatic system.
Levy said the new insight points to two possible treatment pathways: reinforcing lymphocytes so they can withstand the cancer’s countermeasure, or preventing the vesicles from attaching to them at all. “We have a lot of work ahead of us, but it’s clear that this finding could have major therapeutic implications,” she said.
Universities and hospitals involved in the project said additional studies are already in progress to translate the discovery into clinical tools.
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