This researcher is defending the castle - Immune system 1, cancer 0.

This week’s Cool Cancer Find comes from the V Foundation grantee Dr. Lewis Shi's lab at the University of Alabama at Birmingham and the UAB O'Neal Comprehensive Cancer Center .

Adaption is important for survival, even for cancer cells, and the Shi lab studies how cancer cells adapt and thrive under difficult conditions.? To better understand the findings in this study, imagine a video game where players are trying to defend a castle (your body) from invaders (cancer cells).

The defenders of the castle are T cells, a "guardian" cell of the immune system, and they need fuel to fight. Normally, T cells get plenty of oxygen for fuel. But sometimes, T cells have to fight deep inside the castle, where there isn’t much oxygen. This oxygen-poor environment is like the low-oxygen conditions found in some tumors, where blood flow is limited.

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In low-oxygen environments, T cells rely on a different energy source, a protein called HIF1alpha.

Think of HIF1alpha as a T cell’s "low-oxygen mode," allowing the T cell defenders to adapt and continue fighting even with limited fuel. Without HIF1alpha, the T cells lose power, and they can’t perform as effectively. With HIF1alpha, T cells can produce a "supercharge," a signal called IFN-gamma, which strengthens their attacks on cancer cells.

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The Shi lab found that if this “low-oxygen mode” isn’t working properly in T cells, they don’t produce enough IFN-gamma and they become less effective at attacking cancer.

But by adding a ‘boost’ called acetate (like a power-up), even tired T cells in this low-oxygen ‘dungeon’ can regain their strength and ramp up IFN-gamma production, making them better at defending the castle again. Whoohoo! Go T cell defenders!

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Moral of this gaming story? By helping T cells activate their “low-oxygen mode” we can improve immune therapy. Immune system 1, cancer 0.

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Read more about the Shi lab and how they are finding ways to keep these defenders powered up, even in tough conditions at (https://scholars.uab.edu/6643-lewis-zhichang-shi/grants) and find this very cool study at HIF1α-regulated glycolysis promotes activation-induced cell death and IFN-γ induction in hypoxic T cells | Nature Communications