Taking Aim at Inflammation’s Role in Head and Neck Cancer

Inflammation often has a negative connotation, but it is a normal immune response that helps heal injured tissue. When functioning properly, the immune response ramps down once the injury is healed. Sometimes, though, the immune response continues, creating chronic inflammation that can damage healthy cells and, over time, lead to cancer.

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Chronic inflammation is associated with up to 25% of all cancers. Understanding the underlying biological mechanisms that cause the spread or development of cancer due to inflammation is a focus of researchers – and students – at the University of Arizona Health Sciences.

Finding tomorrow’s cancer treatments includes training the next generation of cancer researchers, and thanks to the UArizona Cancer Center’s Integrated Cancer Scholars program, that next generation is already hard at work. Dakota Reinartz, a doctoral student in the UArizona College of Medicine – Tucson, and faculty mentors Justin E. Wilson, PhD, and Julie Bauman, MD, are researching the role inflammation may play in the development of head and neck squamous cell carcinomas.

Understanding inflammation and cancer

“A lot of what we study are the normal immune response events versus the events that lead to chronic inflammation,” said Dr. Wilson, an assistant professor in the Department of Immunobiology. “It is these chronic inflammatory states that have the potential to develop into cancer.”

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In order for cancer to establish itself in the body, two things must happen. First, the cancer cell must acquire mutations that allow it to grow, divide and spread in an abnormal way. Second, the cancer must have a way of compromising or hiding itself from the immune system.

The quest to comprehend what role inflammation plays in that elusive “dance” between the cancer cell and the immune system is the foundation of the project’s research, explained Dr. Bauman, Reinartz’s clinical research mentor and deputy director of the Cancer Center.

“Understanding this interplay is a major area that could improve prevention and therapeutic interventions,” Dr. Bauman said. “This work could point us toward therapeutics that would disrupt the immune shield that the cancer is effectively using to obscure itself.”

Narrowing in on a target

Reinartz is investigating a protein known as AIM2 that is found in immune cells. AIM2 is a pattern recognition receptor, which is a type of protein responsible for kickstarting the immune response against pathogens and cellular distress signals. It does this by activating molecules that are known to cause inflammation.

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"We want to see if AIM2 has a role in the development of cancer," Reinartz said. "Based on preliminary data, we believe it does.”

“The research this team is doing is critical because, as a clinician, I want to know how we can disrupt the process,” Dr. Bauman said. “I see the potential to reverse the inflammatory state associated with head and neck cancer before it does additional damage.”

Inflammation is commonly associated with cancers along the gastrointestinal (GI) tract, including the oral cavity, esophagus and gut. Head and neck cancers, in particular, have devastating and lasting impacts on patients. Vision, hearing, taste, smell and speech can all be affected when a patient undergoes treatment to remove one of these tumors.

“Head and neck cancer is not only life-altering for these patients in terms of their risk of dying, it harms their quality of life profoundly. It takes away those human functions that socially connect us and underlie our social existence,” Dr. Bauman said. “That’s why I am so passionate about preventing these cancers.”

Training the next generation

Reinartz’s work with Drs. Wilson and Bauman is made possible through a National Cancer Institute training grant, known as a T32. The grant supports institutions in developing or enhancing research training opportunities for pre- and postdoctoral fellows in cancer research. The Cancer Center used the funding to establish the Integrated Cancer Scholars program.

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Anne E. Cress, PhD, a UArizona Cancer Center member and senior associate dean for academic faculty and basic science research at the UArizona College of Medicine – Tucson, co-leads the training program.

“A number of different types of students come to me,” Dr. Cress said. “They have very different backgrounds, but they have one thing in common. They want to learn, they’re creative, and they’re critical thinkers. But the way they approach the same problem is very different.”

Reinartz is one of six students participating in the program this year. He hopes to combine his lab experiences with his educational background in biology to focus on a future career as a cancer immunologist.

“The T32 program is training me to become a better scientist, and it is helping me to write my own grant, and hopefully it will be something that can help me get a fellowship down the line,” Reinartz said. “It would be great if this work we are doing in the lab translates into real relevance in the clinical setting.”