Why some triple-negative breast cancers respond to radiation plus immunotherapy and others resist
Project 2: Determinants of Response and Resistance to DNA-Damaging Radiation Plus Immunotherapy Combinations in Triple Negative Breast Cancer
This project looks at whether patterns of tumor cell death and immune signals can predict and improve responses to radiation combined with anti-PD1 immunotherapy for people with early-stage triple-negative breast cancer that has spread to lymph nodes.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of North Carolina Chapel Hill NIH-funded |
| Lab location | 1 site (Chapel Hill, United States) |
| Project ID | NIH-11181663 on NIH RePORTER |
What this research studies
From a patient's perspective, researchers will analyze tumor, lymph node, and blood samples taken before and after treatment from people in a preoperative anti-PD1 trial with or without radiation, while also using genetically engineered mouse models to test mechanisms. They will develop a gene signature that indicates whether tumors undergo necroptosis, a form of DNA-damage cell death, and see if that signature predicts immune changes in the tumor environment. The team will look for T and B cell responses against tumor neoantigens and test whether giving a neoantigen vaccine can help overcome resistance to radiation plus immunotherapy. The overall goal is to guide more personalized chemo‑immunotherapy combinations that limit resistance and treatment-related toxicity.
Who could benefit from this research
Good fit: Ideal candidates are people with early-stage triple-negative breast cancer with lymph node involvement who are eligible for preoperative anti-PD1 therapy with or without radiation and willing to give tumor and blood samples.
Not a fit: Patients with hormone receptor–positive or HER2-positive breast cancer, widely metastatic disease beyond regional lymph nodes, or those not receiving anti-PD1 or radiation would be unlikely to directly benefit from this project.
Why it matters
Potential benefit: If successful, this work could help predict who will benefit from radiation plus anti-PD1 and guide personalized additions (like neoantigen vaccines) to overcome resistance.
How similar studies have performed: Some prior studies show radiation plus anti-PD1 can boost immune responses and links between DNA damage-induced necroptosis and tumor immunity exist, but using neoantigen vaccines to overcome resistance in TNBC is still experimental.
Where this research is happening
Chapel Hill, United States
- Univ of North Carolina Chapel Hill — Chapel Hill, United States (Active)
Researchers
- Principal investigator: Gupta, Gaorav P. — Univ of North Carolina Chapel Hill
- Study coordinator: Gupta, Gaorav P.
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.