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- Title
Pools of programmed death-ligand within the oral cavity tumor microenvironment: Variable alteration by targeted therapies.
- Authors
Shah, Sujay; Caruso, Andria; Cash, Harrison; Waes, Carter Van; Allen, Clint T.
- Abstract
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
- Subjects
LIGANDS (Biochemistry); ORAL cancer; INTERFERONS; SUPPRESSOR cells; SMALL molecules
- Publication
Head & Neck, 2016, Vol 38, Issue 8, p1176
- ISSN
1043-3074
- Publication type
Article
- DOI
10.1002/hed.24269