The aryl hydrocarbon receptor suppresses immunity to oral squamous cell carcinoma through immune checkpoint regulation
Jessica E. Kenison, Zhongyan Wang, Kangkang Yang, Megan Snyder, Francisco J. Quintana, David H. Sherr
Abstract
Significance Immune checkpoint inhibitors have emerged as critical therapeutics for several cancer types, including head and neck squamous cell carcinoma. However, enthusiasm remains constrained by the fact that only a minority of patients benefit. Therefore, there is a need to identify new immunotherapy targets. Here, we provide evidence supporting our hypothesis that the aryl hydrocarbon receptor (AhR) influences multiple immune checkpoints in a model of oral squamous cell carcinoma (OSCC). Remarkably, transplant of AhR-deleted OSCC cells generates completely protective tumor immunity characterized by a decrease in multiple immune checkpoints (PD-L1, CD39, CTLA4, PD1, and Lag3) on malignant and/or immune cells. These results have important implications for understanding the biology of cancer immunosuppression and for targeting the AhR for cancer immunotherapy.