Boosting immune cells against cancer by adjusting one‑carbon metabolism
Defining mechanisms to promote antitumor immunity by modulating one-carbon metabolism
['FUNDING_R01'] · HARVARD MEDICAL SCHOOL · NIH-11258538
This project looks at whether boosting one‑carbon metabolism with formate can help CD8+ immune cells work better with PD‑1 blocking cancer immunotherapy.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | HARVARD MEDICAL SCHOOL (nih funded) |
| Locations | 1 site (BOSTON, UNITED STATES) |
| Trial ID | NIH-11258538 on ClinicalTrials.gov |
What this research studies
Researchers found that the one‑carbon (1C) metabolic pathway, which uses serine and glycine to make building blocks and antioxidants, is highly induced when T cells activate but is limited inside tumors. They will test whether giving formate to restore 1C metabolism helps CD8+ T cells clear tumors and improves responses to anti‑PD‑1 (PD‑L1) immunotherapy. The team will use mouse tumor models, transcriptional and epigenetic profiling (including ATAC‑seq), and conditional genetic tools to define how formate changes T cell function. Results will guide whether metabolic supplementation could be moved toward combination therapies for cancer patients.
Who could benefit from this research
Good fit: Patients receiving PD‑1/PD‑L1 checkpoint immunotherapy, especially those with cancers that respond poorly to these drugs, would be the most relevant group.
Not a fit: Patients whose cancers are not treated with PD‑1/PD‑L1 therapies or who cannot tolerate metabolic supplements may be unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this could increase the number of patients who respond to PD‑1/PD‑L1 immunotherapy by strengthening tumor‑killing T cells.
How similar studies have performed: Preclinical mouse studies by the investigators showed that formate supplementation improved tumor clearance with anti‑PD‑1, but this metabolic combination approach is novel and has not yet been tested in humans.
Where this research is happening
BOSTON, UNITED STATES
- HARVARD MEDICAL SCHOOL — BOSTON, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: SHARPE, ARLENE H. — HARVARD MEDICAL SCHOOL
- Study coordinator: SHARPE, ARLENE H.
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.