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Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment : Beyond Immune Evasion
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Title: | Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment : Beyond Immune Evasion |
Authors: | Dong, Peixin Browse this author →KAKEN DB | Xiong, Ying Browse this author | Yue, Junming Browse this author | Hanley, Sharon J. B. Browse this author →KAKEN DB | Watari, Hidemichi Browse this author →KAKEN DB |
Keywords: | PD-L1 | CD274 | metastasis | EMT | cancer stem cells | microRNA |
Issue Date: | 19-Sep-2018 |
Publisher: | Frontiers Media |
Journal Title: | Frontiers in Oncology |
Volume: | 8 |
Start Page: | 386 |
Publisher DOI: | 10.3389/fonc.2018.00386 |
Abstract: | Although the role of PD-L1 in suppressing the anti-tumor immune response is extensively documented, recent discoveries indicate a distinct tumor-intrinsic role for PD-L1 in modulating epithelial-to-mesenchymal transition (EMT), cancer stem cell (CSC)-like phenotype, metastasis and resistance to therapy. In this review, we will focus on the newly discovered functions of PD-L1 in the regulation of cancer development, describe underlying molecular mechanisms responsible for PD-L1 upregulation and discuss current insights into novel components of PD-L1 signaling. Furthermore, we summarize our current understanding of the link between PD-L1 signaling and the EMT program as well as the CSC state. Tumor cell-intrinsic PD-L1 clearly contributes to cancer stemness, EMT, tumor invasion and chemoresistance in multiple tumor types. Conversely, activation of OCT4 signaling and upregulation of EMT inducer ZEB1 induce PD-L1 expression in cancer cells, thereby suggesting a possible immune evasion mechanism employed by cancer stem cells during metastasis. Our meta-analysis demonstrated that PD-L1 is co-amplified along with MYC, SOX2, N-cadherin and SNAI1 in the TCGA endometrial and ovarian cancer datasets. Further identification of immune-independent PD-L1 functions and characterization of crucial signaling events upstream or downstream of PD-L1 in diverse cancer types and specific cancer subtypes, would provide additional targets and new therapeutic approaches. |
Rights: | http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/71646 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 董 培新
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