cancer

Professor Receives $2.3M NIH Grant to Study Immune Responses to Oral Cancers

The National Institute of Environmental Health Sciences award will help fund David Sherr’s research into the mechanisms of immunosuppression in oral cancers.

David Sherr, professor of environmental health and director of the Sherr Laboratory at the School of Public Health, has received a $2.3 million grant from the National Institute of Environmental Health Sciences to study mechanisms of immunosuppression in oral cancer.

The five-year grant, totaling $2,313,925, will enable Sherr to continue his groundbreaking research on the aryl hydrocarbon receptor (AhR)—a protein that mediates the adverse effects of several environmental chemicals—and its role in the development of oral squamous cell carcinoma (OSCC).

Last year, Sherr led a study published in the journal Proceedings of the National Academy of Science, that identified for the first time that the AhR regulates immune responses in OSCC, and that removing it from malignant cells can effectively prevent the formation of tumors.

The new project will further explore how the AhR contributes to the suppression of otherwise effective anti-tumor immune responses, and this insight will lend important implications for environmental science, immunotoxicology, and immunotherapy.

“This grant will enable us to determine how cancers beat down the immune system, enabling the cancers to grow and metastasize with impunity,” says Sherr. “Thus far, we have shown that cancer cells inappropriately activate a natural immune feedback pathway that has evolved to prevent autoimmunity, an immune response against the hosts own tissue, and to shut down responses to infections once the infections have been cleared. In essence, cancers hijack the normal process of immune regulation to enable their survival.”

Immunotherapies for oral cancers have improved drastically, but they still only benefit a minority of patients—about 30 percent. More broadly, only 40-50 percent of patients with head and neck squamous cell carcinoma survive for five years. The researchers hope to fill this critical gap in knowledge to better understand oral cancers, which are more than twice as common in men (1 in 60) than women (1 in 140). 

“Perhaps most importantly, we are testing novel immunotherapeutics in the hopes of either treating cancers or preventing them entirely by taking the brakes off of the immune system,” he says.

Prior to its research on AhR and oral cancers, the Sherr Lab was also the first to demonstrate dramatically high levels of the AhR in breast cancer.

Sherr is a co-director of the Cancer Interception Group in the BU-BMC Cancer Center and director of the Find the Cause Breast Cancer Foundation Research Consortium. He is also the former and founding director of the BU Flow Cytometry Core, former director of the BU Immunology Training Program, and former director of the Boston University Superfund Research Program.