Blocking PD-L1 cell signaling to boost immunotherapy for head and neck cancer

Targeting PD-L1 interactome signaling to enhance immunotherapy efficacy in head and neck squamous cell cancer

NIH-funded research University of Colorado Denver · NIH-11226266

This project tests whether stopping a cancer cell protein called PD-L1 and blocking a connected pathway (STAT3) can help immunotherapy work better for people with head and neck squamous cell cancer.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUniversity of Colorado Denver NIH-funded
Lab location1 site (Aurora, UNITED STATES)
Project IDNIH-11226266 on NIH RePORTER

What this research studies

From a patient point of view, researchers are looking at how PD-L1 inside cancer cells sends signals that help tumors grow and avoid the immune system. They mapped which proteins bind PD-L1 inside cells and found partners that stabilize STAT3, a driver of tumor growth. In laboratory models and humanized mice with both HPV-positive and HPV-negative tumors, the team combined PD-L1 blockade with STAT3 inhibitors to try to get durable tumor control. The work is preclinical but focused on approaches that could be translated into combination treatments for people whose cancers do not respond to current PD-1/PD-L1 immunotherapies.

Who could benefit from this research

Good fit: Ideal candidates would be people with head and neck squamous cell carcinoma (HPV-positive or HPV-negative), especially those with recurrent or metastatic disease who have had limited benefit from current PD-1/PD-L1 therapies.

Not a fit: People without head and neck squamous cell carcinoma, or whose tumors do not depend on PD-L1/STAT3 signaling or who cannot tolerate STAT3-targeting drugs, are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this work could make immunotherapy effective for more people with head and neck squamous cell carcinoma by targeting PD-L1 signaling and STAT3 together to slow tumor growth and improve outcomes.

How similar studies have performed: PD-1/PD-L1 inhibitors have helped some patients with head and neck cancer, but combining inhibition of PD-L1 intracellular signaling with STAT3 blockade is a newer, mainly preclinical strategy that has shown promise in mouse models but is not yet proven in people.

Where this research is happening

Aurora, UNITED STATES

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.