DoD Award Funds Research on Immunotherapy Resistance in Head, Neck Cancer

CINCINNATI—Head and neck cancers are the sixth most common cancers worldwide. Difficult to treat and with poor patient outcomes, these types of cancers are twice as common in veterans because of factors like increased tobacco and alcohol use.

Immunotherapy, a treatment strategy which involves arming the patient’s own T lymphocytes—a type of immune cell—to destroy cancer, has been shown to be effective in this type of cancer, but many patients do not respond to this treatment.

Now, thanks to a $1 million grant from the U.S. Department of Defense, researchers at the University of Cincinnati (UC) College of Medicine will look closely at the reason why patients with this type of cancer experience resistance to immunotherapy treatments.

"We believe that immunotherapy, specifically in this case an antibody against PD1, a protein expressed on the membrane of T lymphocytes, stops tumor growth by activating pathways that encourage immune cells to enter into the tumor and kill cancer cells,” says Laura Conforti, PhD, professor of medicine and a researcher within the UC Cancer Institute. "Resistance develops because, in some patients, these beneficial effects of immunotherapy do not take place, and/or immunotherapy stimulates other mechanisms that suppress the ability of immune cells to function.”

In the study, researchers will be using blood and tumor samples from patients with head and neck cancers who have been treated with immunotherapy containing the PD1 antibody. Additionally, they will use animal models and cell cultures to test whether combination therapies of the Food and Drug Administration-approved immunotherapeutic PD1 antibody with drugs that act on the pathways being studied can be more beneficial than with just the PD1 antibody alone.

Conforti says some of these pathway-targeting drugs are already tested for use in humans.

"The hope is that these studies will set the stage for future clinical trials and that in 3 to 4 years we will be able to test these new combination therapies in patients,” she says. "Ultimately, these studies will help us understand why immunotherapy works in some people and why it doesn’t work in others and will help in developing new therapies for head and neck cancer patients. We also anticipate that the results of our studies will have a broad application to many other cancers.

"It is worth noting that veterans often carry more medical conditions than the general population, making treatment sometimes difficult. However, immunotherapy has relatively mild side effects unlike classic chemotherapy and radiation treatment. Our studies could eventually lead to increased use of immunotherapy and provide treatments that help patients while reducing the stress of their families especially in the veteran and active military population.”

The grant is a 3-year Translational Team Science Award. Co-principal investigators on the award along with Conforti are Trisha Wise-Draper, MD, PhD, UC Department of Internal Medicine, Division of Hematology Oncology, and Edith Janssen, PhD, UC Department of Pediatrics, Cincinnati Children’s Hospital Medical Center.