By Sola Ogundipe
In a breakthrough that could turbocharge cancer treatment, scientists at Weill Cornell Medicine have uncovered how tumours drain the strength of the body’s immune fighters and how to stop it.
The study, published in Nature Immunology, reveals that cancer cells use a molecular signal to push T cells into exhaustion, weakening their ability to attack. Blocking that signal, researchers found, keeps T cells energized and dramatically improves their tumour-fighting power.
“Our dream is to revive exhausted T cells so the immune system itself can defeat cancer. This discovery brings that future closer. T cell exhaustion is a major obstacle in modern immunotherapy. Even when patients initially respond well, their T cells can eventually burn out, reducing the effectiveness of treatment,” said co-senior author Dr. Taha Merghoub, a leading cancer immunologist at Weill Cornell Medicine.
The new study zeroes in on CD47, a protein known as the “don’t eat me” signal that cancer cells use to evade immune attack. Researchers were surprised to find that T cells also produce CD47—and when they become exhausted, CD47 levels shoot up. Experiments in mice showed that animals lacking CD47 developed slower-growing tumours, suggesting that high CD47 levels help shut down the immune response from within. Tumours appear to worsen this effect by releasing thrombospondin-1, a protein that binds to CD47 and further weakens T cells.
“That was the eureka moment. Remove CD47 or thrombospondin-1, and T cells stay strong,” Merghoub said.
To block the interaction, the team tested a peptide called TAX2, which prevents CD47 and thrombospondin-1 from linking. Treated mice saw slower melanoma and colorectal tumour growth, more active T cells, and stronger immune signals. TAX2 also boosted the performance of PD1 immunotherapy, a frontline cancer treatment.
Lead author Dr. Chien-Huan Weng said the peptide acted as “proof-of-concept” and that work is underway to develop safe, targeted ways to block the pathway in patients. Researchers say the approach could become a powerful new therapy on its own or help patients
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