What makes cancer-fighting T cells become exhausted
Uncovering the metabolic underpinnings of T cell exhaustion
This project looks at how stress inside immune T cells causes them to stop fighting cancer and aims to guide ways to keep them active for people getting immunotherapy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pittsburgh at Pittsburgh NIH-funded |
| Lab location | 1 site (Pittsburgh, United States) |
| Project ID | NIH-11141827 on NIH RePORTER |
What this research studies
Researchers are studying how metabolic stress and damaged mitochondria drive T cells into a dysfunctional, "exhausted" state, focusing on reactive oxygen species (ROS) and metabolic signals like aconitase and acetyl-CoA. The team will use lab-grown immune cells, animal models, and molecular analyses to trace how ROS changes signaling and metabolism in T cells. They will test whether lowering ROS or altering metabolic pathways can shift exhausted cells back toward more functional, tumor-killing states. Results are intended to inform new approaches to improve responses to checkpoint inhibitor immunotherapies.
Who could benefit from this research
Good fit: People with cancer, particularly those receiving or who have not responded to checkpoint inhibitor immunotherapy, are the most relevant candidates for potential future applications.
Not a fit: People without cancer or those not treated with immune-based therapies are unlikely to receive direct benefit from this work.
Why it matters
Potential benefit: If successful, this work could lead to metabolic or antioxidant-based approaches that help more patients respond to cancer immunotherapy.
How similar studies have performed: Prior laboratory studies have shown that reducing mitochondrial stress and ROS can restore T cell function, but clinical benefit in patients has not yet been established.
Where this research is happening
Pittsburgh, United States
- University of Pittsburgh at Pittsburgh — Pittsburgh, United States (Active)
Researchers
- Principal investigator: Delgoffe, Greg M. — University of Pittsburgh at Pittsburgh
- Study coordinator: Delgoffe, Greg M.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.