What is it about?
Cancer cells can trick the body’s immune system into ignoring them. One way they do this is by displaying a molecule called phosphatidylserine (PS) on their surface, an evolutionarily conserved “anti-inflammatory” signal normally used by dying cells to tell immune cells “don’t attack.” This study discovered that a membrane protein called TMEM16F is responsible for exposing PS on tumor cells. This “fake death” signal changes nearby immune cells, turning them from attackers into protectors of the tumor. When TMEM16F was blocked or removed, the immune system became reactivated and attacked the cancer more effectively, dramatically inhibiting tumor growth. These results suggest that targeting TMEM16F leads to new cancer immunotherapies that make existing treatments more effective.
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Why is it important?
This research identifies a completely new mechanism of immune evasion: cancer cells using a normal self-protection signal to mimic dying cells and suppress anti-tumor immunity. While most immunotherapies target proteins on immune cells, our work shifts the focus to a membrane lipid-regulating protein on tumor cells, providing a fresh direction for therapy design. The study is especially timely given the urgent need for new strategies to overcome resistance to checkpoint blockade and other immunotherapies.
Perspectives
This publication represents a milestone in my effort to connect membrane biology with immunology. My career has focused on how ion channels and lipid scramblases regulate membrane dynamics. Discovering that TMEM16F, a protein I have studied for years, plays a central role in controlling tumor-immune interactions was deeply rewarding. It highlights how fundamental cell biology can lead to new translational insights. I believe this work opens an exciting avenue for developing PS-targeted cancer therapies that can work alongside existing immunotherapies to improve patient outcomes.
Professor Yang Zhang
Read the Original
This page is a summary of: TMEM16F phospholipid scramblase regulates tumorigenesis by modulating the tumor immune microenvironment, Proceedings of the National Academy of Sciences, October 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2513910122.
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