Stopping chemotherapy from weakening immunotherapy in non-small cell lung cancer
Official title: Identifying and targeting a novel mechanism of chemotherapy-induced immunotherapeutic resistance in non-small cell lung cancer
Funded at University of Louisville · NIH-11307067 · Data updated 2026-11-12
This project looks at whether common chemotherapy makes lung tumors release substances that turn off immune cells and whether blocking that process could help immunotherapy work better for people with non-small cell lung cancer.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Louisville NIH-funded |
| Lab location | 1 site (Louisville, United States) |
| Project start | April 1, 2023 |
| Project end | March 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $352,896 |
| NIH project number | 5R01CA272772-04 |
| Project ID | NIH-11307067 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates would be people with non-small cell lung cancer who are receiving or likely to receive platinum-based chemotherapy together with PD-1/PD-L1 immunotherapy, or patients willing to donate tumor tissue for analysis.
✕Less likely to help
People without non-small cell lung cancer, those not treated with platinum chemotherapy, or patients whose tumors do not use the adenosine/CD73 pathway may not benefit from these findings.
What this research studies
Researchers will follow a step-by-step pathway they found in the lab where cisplatin causes tumor cells to make prostaglandin E2, which then increases CD73 on certain immune cells and leads to production of adenosine that suppresses CD8 T cells. They will use tumor samples, cell experiments, and mouse models to trace each step and measure how the tumor environment changes after chemotherapy. The team will test drugs or antibodies that block PGE2 signaling, CD73 activity, or adenosine receptors to see if T cell function and anti-tumor immunity recover. Results will be compared with patient tumor tissue to make sure the pathway is relevant to people with non-small cell lung cancer.
Why it matters
Potential benefit: If successful, this work could lead to new treatments given alongside chemotherapy that prevent chemo from blunting immunotherapy, improving responses in non-small cell lung cancer.
How similar studies have gone: Early laboratory work and some early-phase trials targeting CD73 or adenosine signaling have shown promise, but applying these approaches specifically to cisplatin-driven resistance in NSCLC is relatively new.
Where this research is happening
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University of Louisville
Louisville, United States Active
Researchers
- Principal investigator: Yaddanapudi, Kavitha — University of Louisville
- Study coordinator: Yaddanapudi, Kavitha
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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.