Promising new target for oral cancer treatment
NIEHS-funded researchers identified how the aryl hydrocarbon receptor (AhR), an environmental chemical receptor, suppresses the body’s immune response to oral cancer. They also discovered that removing AhR from cancer cells stops tumor growth. Results identify a new target for treatments that help the immune system fight cancer.
The researchers used gene-editing techniques to delete AhR from mouse oral cancer cells and then transplanted the altered cancer cells into normal mice. They measured tumor growth and compared changes in gene expression and immune response between AhR-negative and unaltered tumor cells.
While unaltered tumor cells showed robust growth in mice, mice with the AhR-negative cells were completely tumor free within two weeks. This lack of tumor growth was accompanied by an increase in immune cells and a decrease in multiple immune checkpoint proteins. Immune checkpoints can block immune cells from killing tumor cells. Furthermore, when mice previously injected with AhR-negative cells were given the unaltered tumor cells 100 days later, they had a strong immune response and zero tumor growth, suggesting a long-term antitumor immune response.
According to the authors, study results highlight the role of AhR in reducing tumor immune response and point to AhR as a promising target for cancer immunotherapy.
Citation: Kenison JE, Wang Z, Yang K, Snyder M, Quintana FJ, Sherr DH. 2021. The aryl hydrocarbon receptor suppresses immunity to oral squamous cell carcinoma through immune checkpoint regulation. Proc Natl Acad Sci U S A 118(19):e2012692118.