Head and neck cancer is a devastating disease that is becoming increasingly common worldwide. Although immunotherapy has transformed cancer treatment by helping the immune system recognize and attack tumors, these therapies are effective in only a small percentage of head and neck cancer patients. Nearly 85% of patients do not benefit, leaving many with limited treatment options. Understanding why these cancers resist immunotherapy is one of the most urgent challenges in the field.
Dr. Wheeler’s research focuses on a protein called EphA2, which is found at high levels in most head and neck cancers. His team has discovered that EphA2 helps tumors hide from the immune system in two important ways: First, tumors with high EphA2 levels contain fewer immune cells capable of killing cancer and more cells that suppress immune responses.
Second, EphA2 helps tumors build a dense collagen barrier around themselves, which acts like a protective shield, physically blocking immune cells from entering the tumor and reducing the effectiveness of immunotherapy.
In laboratory and animal studies, blocking EphA2 breaks down this barrier and allows immune cells to reach and attack the tumor more effectively. Dr. Wheeler plans to investigate how EphA2 and a related protein called DDR1 work together to control collagen and immune cell access, while also testing new treatment combinations and studying patient tumor samples.
This work could lead to powerful new strategies that make immunotherapy effective for far more patients and lay the groundwork for future clinical trials.
Project and Grants: EphA2-DDR1 axis promotes collagen remodeling and immune exclusion in head and neck cancer
