Scientists break new ground in cancer fight by 'reinvigorating' T cells

Exhausted T-cells can join forces with cancer

"We often think about our immune system in absolutes: Certain types of cells are 'good,' and some are 'bad,'" said senior author Greg Delgoffe Ph.D., in a press release, an associate professor of immunology at Pitt's School of Medicine.

The new study discovered that when worn-out T-cells invade tumors, they actively switch off other cells in the area by altering the environment around them. "In other words, exhausted T-cells aren't just failing to work for us; they are actively working against us," said Delgoffe. 

"The key takeaway from our work is that our immune system is critically sensitive to its local environment. In the right environment, cells typically thought to be anti-cancer can switch sides and work against us," he explained.

Critically, the argument that worn-out T-cells in cancer work against us also opens up new immunotherapy treatment options. This includes creating drugs that target the mechanism responsible for switching sides or creating better T-cells for cell-based therapies.

"While the immunotherapy field has rightfully been focused on correcting T-cell loss of anti-cancer functions, our efforts show we should also be studying potential new behaviors gained by these cells," revealed Paolo Vignali, Ph.D., who directed the new study. He is also a participant in Pitt's Medical Scientist Training Program. 

Reversing T-cells' function is 'exciting'

The team did this by showing that targeting low oxygen levels decreased the suppressive nature of tired T cells, improving the immune response to cancerous tumors. 

The finding that 'reversing' anti-inflammatory functions in exhausted T-cells is particularly exciting. Vignali explained this because "many large, sophisticated studies have taught us that most features of exhausted T cells are irreversible — they are stuck being poor tumor killers."

Here, the new study's data shows that scientists can target the battlefield instead of specifically targeting T-cells, shifting the balance in favor of immune cells. The researchers argue that this approach is feasible in even large, aggressive tumors.

Clinical trials are underway 

The team in Pittsburgh is now conducting several clinical trials involving these environment-modulating medications on cancer patients. "The next big question will be whether we can reverse the immunosuppressive character of exhausted T-cells in these patients," said Delgoffe.

He added that the group is eager to create medicines targeting patients' suppressive nature of T-cells. Interestingly, these would be examined with diseases other than cancer.

Exhausted T-cells can also be seen in the gut, autoimmune illnesses like lupus and Type 1 diabetes, and persistent infections like hepatitis and HIV.

"Discovering the role for these cells and their suppressive character in other contexts will be a new direction for this research," Delgoffe concluded. 

What are exhausted T-cells?

In case you've reached this point and are not familiar with what exhausted T-cells (T stands for Thymus) are, here's a quick run-through.

Exhausted T-cells are the immune system's warriors that fight abnormal, or 'foreign,' cells nonstop. Our immune system uses T-cells to track down and eliminate these cells- which can be malignant or virally contaminated. T-cells are designed to battle until all abnormal cells have been eliminated. 

Still, T cells can malfunction, and abnormal cells can persist in conditions like cancer, where such cells outpace the immune system. As a result, T-cells progressively lose their combating effectiveness and can be described as 'exhausted.'