Aryl hydrocarbon receptor suppresses immunity to oral cancer through immune checkpoint regulation

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A new Boston University School of Public Health (BUSPH) study has identified for the first time how the aryl hydrocarbon receptor (AhR), an environmental chemical receptor, drives immunosuppression in oral squamous cell carcinoma (OSCC)–and that its removal from malignant cells can result in tumor rejection.

Published in the journal Proceedings of the National Academy of Sciences, the study findings provide new insight into the biology of cancer immunosuppression, and identify a new target for cancer immunotherapy treatment.

Immune checkpoint inhibitors (immunotherapy drugs) are some of the most important treatments that have emerged for treating many cancers, including OSCC. Targeting immune checkpoint molecules such as PD-1, PD-L1 and CTLA4 has demonstrated that immunosuppression plays a significant role in OSCC pathology. But immune checkpoint inhibitors are only effective for about 30 percent of cancer patients, so there is a critical need for researchers to identify new immunotherapy targets.

“This study illustrates how studying the basic science of common environmental pollutants’ suppression of the immune system can result in a hugely impactful new approach to cancer prevention and immunotherapy,” says Dr. David Sherr, study lead author and a professor of environmental health at BUSPH. The study was conducted in his lab, the Sherr Lab, located in the Department of Environmental Health at SPH.

Dr. Zhongyan Wang, a postdoctoral fellow at SPH and a co-author of the study, used gene-editing techniques to delete a single gene that encodes the AhR, an environmental chemical receptor, from highly malignant mouse oral cancer cells.

After these minimally altered cancer cells were transplanted into normal mice, Jessica Kenison-White, first author of the study, measured tumor growth and compared the strength and nature of the immune response to the cancer cells with the ineffective immune response to the unaltered cancer cells, using digital…