Open AccessThe aryl hydrocarbon receptor suppresses immunity to oral squamous cell carcinoma through immune checkpoint regulation
Author(s) -
Jessica E. Kenison,
Zhongyan Wang,
Kangkang Yang,
Megan Snyder,
Francisco J. Quintana,
David H. Sherr
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2012692118
Subject(s) - aryl hydrocarbon receptor , immune checkpoint , cancer research , immune system , biology , t cell , immunotherapy , immunology , immunity , transcription factor , biochemistry , gene
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.