Journal
ORAL ONCOLOGY
Volume 51, Issue 3, Pages 221-228Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.oraloncology.2014.11.014
Keywords
Head and neck cancer; Squamous cell carcinoma; PD-L1 (B7-H1, CD274); Carcinogenesis; Immune regulation; Immunotherapy; Keratinocytes; Epithelial-mesenchymal transition
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Funding
- Japan Society for the Promotion of Science (JSPS) [20249075, 23249082, 26253086]
- Grants-in-Aid for Scientific Research [26253086, 20249075, 23249082] Funding Source: KAKEN
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Recent clinical results for PD-1 blockade therapy have demonstrated durable tumor control with minimal immune-related adverse effects. PD-L1 is induced in non-lymphoid tissue cells and tumor cells, in addition to tissue-recruiting immune cells, under inflammatory conditions triggered by several cytokines, especially IFN-gamma, and exogenous stimuli delivered by pathogen-associated molecular patterns. Receptor-mediated signaling molecules that affect the cell cycle, proliferation, apoptosis, and survival (including NF-kappa B, MAPK, PI3K, mTOR, and JAK/STAT) are involved in PD-L1 induction. PD-L1 expression in tumor cells is also triggered by the signals described above, but in some instances, intrinsic cell alteration associated with carcinogenesis contributes to PD-L1 induction. The tumor suppressor genes PTEN and Lkb1 and epithelial-mesenchymal transition-related molecules are also involved in the regulation of PD-L1 expression. Notably, squamous cell carcinoma of the head and neck (SCCHN) often exhibits both host immunosuppression and cytogenetic alternations of tumor cells. Precise understanding of how PD-L1 expression is controlled will allow the development of effective approaches to PD-1 blockade therapy for patients with SCCHN. (C) 2014 The Authors. Published by Elsevier Ltd.
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