Pools of programmed death‐ligand within the oral cavity tumor microenvironment: Variable alteration by targeted therapies
S Shah, A Caruso, H Cash, CV Waes, CT Allen - Head & neck, 2016 - Wiley Online Library
S Shah, A Caruso, H Cash, CV Waes, CT Allen
Head & neck, 2016•Wiley Online LibraryBackground Enhanced understanding of programmed death‐ligand (PD‐L) expression in
oral cancer is important for establishing rational combinations of emerging immune
checkpoint and molecular targeted therapies. Methods We assessed PD‐L and interferon
(IFN) expression in immunogenic murine oral cancer‐1 (MOC1) and poorly immunogenic
MOC2 cell models after treatment with mammalian target of rapamycin (mTOR) and MEK1/2
small molecule inhibitors in vitro and in vivo. Results PD‐L1 but not PD‐L2 is expressed on …
oral cancer is important for establishing rational combinations of emerging immune
checkpoint and molecular targeted therapies. Methods We assessed PD‐L and interferon
(IFN) expression in immunogenic murine oral cancer‐1 (MOC1) and poorly immunogenic
MOC2 cell models after treatment with mammalian target of rapamycin (mTOR) and MEK1/2
small molecule inhibitors in vitro and in vivo. Results PD‐L1 but not PD‐L2 is expressed on …
Background
Enhanced understanding of programmed death‐ligand (PD‐L) expression in oral cancer is important for establishing rational combinations of emerging immune checkpoint and molecular targeted therapies.
Methods
We assessed PD‐L and interferon (IFN) expression in immunogenic murine oral cancer‐1 (MOC1) and poorly immunogenic MOC2 cell models after treatment with mammalian target of rapamycin (mTOR) and MEK1/2 small molecule inhibitors in vitro and in vivo.
Results
PD‐L1 but not PD‐L2 is expressed on MOC1 and 2 cells and is type I and II IFN‐dependent. PD‐L1 is differentially expressed on cancer and endothelial cells and infiltrating myeloid‐derived suppressor cells, macrophages, and regulatory T cells (Tregs) in highly and poorly immunogenic tumors. PD‐L1 expression is variably altered after treatment with inhibitors in vivo, with an imperfect relationship to alterations in IFN levels in the tumor microenvironment.
Conclusion
PD‐L1 expressed on cancer and infiltrating immune cells is variably altered by targeted therapies and may, in part, reflect changes in tumor IFN. © 2016 Wiley Periodicals, Inc. Head Neck 38:1176–1186, 2016
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