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T Cells Can Auto-Activate To Fight Tumors

Super-resolution image of a group of killer T cells (green and red) surrounding a cancer cell (blue, center).
Super-resolution image of a group of killer T cells (green and red) surrounding a cancer cell (blue, center). Credit: National Institutes of Health, Alex Ritter, Jennifer Lippincott Schwartz, and Gillian Griffiths

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When you need a bit of motivation, it often has to come from within. New research suggests cancer-fighting immune cells have found a way to do just that.

Scientists at University of California San Diego have discovered a property of T cells that could inspire new anti-tumor therapeutics. Through a previously undescribed form of cell auto-signaling, T cells were shown to activate themselves in peripheral tissues, fueling their ability to attack tumors.

The study, published May 8, 2023 in Immunity, was led by study first author and postdoctoral fellow Yunlong Zhao, PhD, and co-senior authors Enfu Hui, PhD, professor in the School of Biological Sciences at UC San Diego and Jack D. Bui, MD, PhD, professor of pathology at UC San Diego School of Medicine.

The researchers then confirmed that this auto-stimulation was indeed effective in boosting T cell function and slowing tumor growth in a mouse model of cancer.

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“When a T cell exits a lymph organ and enters a tumor environment, it’s like leaving home and going for a long trek in the woods,” said Bui. “The same way a hiker brings snacks to sustain them through the trip, the T cells bring their own signal to keep them going. Now the exciting question is, how much farther will they go if we can provide more food?” 

Refueling the T cells could be achieved by either providing more sources of B7 in the lymph organs or in the tumor itself. Another option, the authors say, would be to develop a cell therapy in which engineered T cells with enhanced auto-signaling capabilities were delivered directly to a patient. 

The researchers also suggest this system could be used as a cancer biomarker, in that patients whose tumors contain many T cells with B7 may be doing better at fighting the disease. 

On the other hand, in patients with autoimmune diseases such as lupus or multiple sclerosis, physicians could prescribe endocytosis inhibitors to prevent the cell from forming concavities, effectively blocking the B7:CD28 interaction to reduce overactive T cell function. 

“We’ve found a way that T cells are able to live outside of their normal homes and survive in the foreign environment of a tumor, and we can now develop clinical strategies for increasing or decreasing these pathways to treat disease,” said Hui. 

Reference: Zhao Y, Caron C, Chan YY, et al. cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8+ T cell function and anti-tumor immunity. Immunity. 2023;0(0). doi: 10.1016/j.immuni.2023.04.005

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