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Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment : Beyond Immune Evasion

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タイトル: Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment : Beyond Immune Evasion
著者: Dong, Peixin 著作を一覧する
Xiong, Ying 著作を一覧する
Yue, Junming 著作を一覧する
Hanley, Sharon J. B. 著作を一覧する
Watari, Hidemichi 著作を一覧する
キーワード: PD-L1
CD274
metastasis
EMT
cancer stem cells
microRNA
発行日: 2018年 9月19日
出版者: Frontiers Media
誌名: Frontiers in Oncology
巻: 8
開始ページ: 386
出版社 DOI: 10.3389/fonc.2018.00386
抄録: 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.
資料タイプ: article
URI: http://hdl.handle.net/2115/71646
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 董 培新

 

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