Why some triple-negative breast cancers respond to radiation plus immunotherapy and others resist
Official title: Project 2: Determinants of Response and Resistance to DNA-Damaging Radiation Plus Immunotherapy Combinations in Triple Negative Breast Cancer
Funded at Univ of North Carolina Chapel Hill · NIH-11181663 · Data updated 2026-11-12
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 start | August 5, 1997 |
| Project end | August 31, 2029 |
| Funding year | 2025 |
| Award (this year) | $350,219 |
| NIH project number | 5P50CA058223-30 |
| Project ID | NIH-11181663 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
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.
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.
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 gone: 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
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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.
Related research
Other NIH-funded projects on the same topics.
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Rac-enhanced CAR-Macrophages against TNBC
A new cell therapy approach uses engineered macrophages with a CAR and Rac2 activation to target and kill triple-negative breast cancer cells expressing CSPG4.
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Determinants of Response to DNA-Damaging Radiation and Immunotherapy in Triple-Negative Breast Cancer
This grant explores why some people with triple-negative breast cancer respond to a combo of radiation, chemotherapy, and immunotherapy and why others don’t, to guide more personalized treatment.
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New immunotherapy combo for hard-to-treat triple-negative breast cancer
Aims to test a combination immunotherapy with JNK inhibitors to improve treatment for people with triple-negative breast cancer.
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Reprogrammed exosome immunotherapy for triple-negative breast cancer
A new treatment approach uses engineered exosomes to stimulate the immune system to fight triple-negative breast cancer in patients.
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Engineered CD4+ T cells targeting KK‑LC‑1 for triple‑negative breast cancer
This project creates engineered CD4+ T cells that recognize the KK‑LC‑1 tumor antigen to help people with HLA‑DR13-positive triple‑negative breast cancer.
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New combination immunotherapy for triple-negative breast cancer
See if adding a drug that blocks the JNK pathway can help immunotherapy work better for people with triple-negative breast cancer.
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.