Blocking a single protein boosts T cell metabolism and tumor-fighting strength. The discovery could lead to next-generation cancer immunotherapies.
Scientists have identified a strategy to greatly enhance the cancer-fighting abilities of the immune system’s T cells. By inhibiting a protein known as Ant2, they succeeded in reshaping how these cells produce and use energy, effectively redesigning their internal power systems.
This adjustment makes T cells stronger, more durable, and more efficient at targeting tumors. The discovery opens new possibilities for therapies that reinforce the body’s natural defenses, offering a more precise and effective form of cancer treatment.
International team leads breakthrough
A recent study suggests the potential for a new wave of cancer therapies that rely on training the immune system to perform more effectively. The work, led by PhD student Omri Yosef and Prof. Michael Berger at the Hebrew University Faculty of Medicine, brought together collaborators including Prof. Magdalena Huber of Philipps University of Marburg and Prof. Eyal Gottlieb of the University of Texas MD Anderson Cancer Center. Their findings show that carefully adjusting immune cell metabolism significantly boosts the cells’ ability to destroy tumors.
Central to the research is a striking observation: when T cells—the immune system’s front-line fighters—are compelled to change the way they generate and manage energy, they become far more adept at recognizing and eliminating cancer cells.
“By disabling Ant2, we triggered a complete shift in how T cells produce and use energy,” explains Prof. Berger. “This reprogramming made them significantly better at recognizing and killing cancer cells.” In simpler terms, blocking this protein forces the immune cells to adapt their metabolism, turning them into stronger, faster, and more aggressive cancer fighters.
Mitochondria as cellular engines
Published in Nature Communications, the study focuses on the mitochondria—the “metabolic hub” of cells. By deliberately disrupting a specific energy pathway inside T cells, the team essentially rewired the cells’ engines, creating a state of heightened readiness and potency. The altered T cells exhibited greater stamina, faster replication, and sharper targeting of cancerous threats.
Perhaps most importantly, the researchers showed that this metabolic rewiring can be triggered not only through genetic modifications but also with drugs—opening the door for potential clinical applications.
This discovery is part of a growing movement in cancer immunotherapy that focuses not only on guiding the immune system but upgrading its inner machinery. While more studies and clinical trials are needed, the implications of this breakthrough are promising: new treatments that harness the body’s own defenses, fine-tuned for peak performance.
“This work highlights how deeply interconnected metabolism and immunity truly are,” says Prof. Berger. “By learning how to control the power source of our immune cells, we may be able to unlock therapies that are both more natural and more effective.”
Reference: “Metabolic reprogramming driven by Ant2 deficiency augments T Cell function and anti-tumor immunity in mice” by Omri Yosef, Leonor Cohen-Daniel, Oded Shamriz, Zahala Bar-On, Wajeeh Salaymeh, Amijai Saragovi, Ifat Abramovich, Bella Agranovich, Veronika Lutz, Joseph Tam, Anna Permyakova, Eyal Gottlieb, Magdalena Huber and Michael Berger, 8 May 2025, Nature Communications.
DOI: 10.1038/s41467-025-59310-3
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