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Pools of programmed death‐ligand within the oral cavity tumor microenvironment: Variable alteration by targeted therapies
Author(s) -
Shah Sujay,
Caruso Andria,
Cash Harrison,
Waes Carter Van,
Allen Clint T.
Publication year - 2016
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.24269
Subject(s) - tumor microenvironment , cancer research , immune system , immune checkpoint , in vivo , immunotherapy , pd l1 , cancer , pi3k/akt/mtor pathway , head and neck squamous cell carcinoma , cancer cell , biology , immunology , microbiology and biotechnology , head and neck cancer , signal transduction , genetics
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