Why a gene called CREB5 can make cancers stop responding to immunotherapy
Investigating CREB5-driven mechanisms of immune therapy resistance
This project is looking at whether tumors that make extra CREB5 drive up collagen to turn off immune cells and cause resistance to anti-PD-1 immunotherapy, with the goal of helping people whose cancers do not respond to these drugs.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Massachusetts General Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11247169 on NIH RePORTER |
What this research studies
Researchers discovered CREB5 as a top hit in a large genetic screen that looked for genes that let tumors evade anti-PD-1 therapy. They will use laboratory tumor models and mice to raise or block CREB5 and measure how immune cells, especially CD8+ T cells, can enter and attack tumors. The team will study changes in gene activity and chromatin (including ATAC-seq and transcriptional profiling) to learn how CREB5 increases collagen and other extracellular matrix factors. They will also test whether removing the collagen receptor LAIR1 or adding a decoy LAIR2 can reverse the immune-blocking effect of CREB5.
Who could benefit from this research
Good fit: People whose cancers did not respond to or stopped responding to immune checkpoint drugs (for example anti-PD-1 therapies) would be most relevant.
Not a fit: Patients whose cancers are controlled by other treatments, those whose tumors do not use immune-checkpoint or collagen/LAIR1 pathways, or those too frail for experimental approaches may not directly benefit from this basic research.
Why it matters
Potential benefit: If successful, this work could point to new ways to prevent or reverse resistance to checkpoint immunotherapy so more cancer patients benefit from these treatments.
How similar studies have performed: Prior preclinical work shows collagen can suppress immune cells through LAIR1 and that blocking LAIR1 or using LAIR2 can restore immune responses in models, but focusing on CREB5 as a driver of this pathway is a newer approach.
Where this research is happening
Boston, United States
- Massachusetts General Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Manguso, Robert Thomas — Massachusetts General Hospital
- Study coordinator: Manguso, Robert Thomas
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.