The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune Checkpoint

Wang, Qingshui; Lin, Wei; Tang, Xiaoqiong; Li, Suhuan; Guo, Libin; Lin, Yao; Kwok, Hang Fai

doi:10.3390/ijms18122540

Cited by 107 publications

(89 citation statements)

References 67 publications

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“…In this way, mutations of the PD‐L1 3'‐UTR can escape these controls and result in excessive PD‐L1 expression (Chen et al, ). Other miRNAs regulate upstream targets in the PD‐L1 pathway, including IFN‐γ, IFNGR‐1, PTEN, IRF‐1, c‐Fos and STAT1, and their dysregulation could also produce an increase in PD‐L1 (Wang et al, ).…”

Section: Pd‐l1 In Cancermentioning

confidence: 99%

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

et al. 2019

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Programmed cell death‐ligand 1 (PD‐L1) is a transmembrane protein that acts as a co‐inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD‐1), is found on immune cells, where binding to PD‐L1 can reduce the proliferation of PD‐1‐positive cells, inhibit their cytokine secretion and induce apoptosis. PD‐L1 in immune‐privileged tissue plays a crucial role in peripheral tolerance. PD‐L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD‐1:PD‐L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD‐L1, including its structure, function and regulation. We also review studies on the overexpression of PD‐L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.

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Section: Pd‐l1 In Cancermentioning

confidence: 99%

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

et al. 2019

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“…[16][17][18][19][20][21][22] MiRs function in part by targeting the 39UTRs of messenger RNAs (mRNAs) for degradation and/or translational repression, and host miRs have been shown to regulate both PD-1 and PD-L1 expression. 23 However, the role of EBV miR in the regulation of PD-L1 and PD-L2 has yet to be established, and its elucidation may have potential therapeutic implications.…”

Section: Introductionmentioning

confidence: 99%

EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2

Cristino

Nourse

West

et al. 2019

Blood

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This article reports a novel mechanism by which Epstein-Barr virus (EBV) microRNA (miRNA) plays a role to fine-tune the expression of LMP1-driven amplification of inhibitory checkpoint programmed death ligand 1 (PD-L1) and PD-L2 in EBV+ diffuse large B-cell lymphoma. Identification and understanding of the immune checkpoint regulation via miRNA may enable potential novel RNA-based therapies to emerge.

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“…Some miRNAs have been found to directly target the 3'-UTR of PD-1 or PD-L1 mRNA, while others miRNAs may regulate PD-1/PD-L1 indirectly via signaling molecules (such as IFN-γ, PTEN, mTOR, STAT and others) [95]. In TNBC cells, miR-195 and miR-497 regulate CD274 (PD-L1) expression by direct targeting [53].…”

Section: Mirna and Immune Checkpoint Regulationmentioning

confidence: 99%

microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics

Maroni

Banfi

Lombardi

2020

IJMS

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Breast cancer is the most common type of cancer in women, and the occurrence of metastasis drastically worsens the prognosis and reduces overall survival. Understanding the biological mechanisms that regulate the transformation of malignant cells, the consequent metastatic transformation, and the immune surveillance in the tumor progression would contribute to the development of more effective and targeted treatments. In this context, microRNAs (miRNAs) have proven to be key regulators of the tumor-immune cells crosstalk for the hijack of the immunosurveillance to promote tumor cells immune escape and cancer progression, as well as modulators of the metastasis formation process, ranging from the preparation of the metastatic site to the transformation into the migrating phenotype of tumor cells. In particular, their deregulated expression has been linked to the aberrant expression of oncogenes and tumor suppressor genes to promote tumorigenesis. This review aims at summarizing the role and functions of miRNAs involved in antitumor immune response and in the metastasis formation process in breast cancer. Additionally, miRNAs are promising targets for gene therapy as their modulation has the potential to support or inhibit specific mechanisms to negatively affect tumorigenesis. With this perspective, the most recent strategies developed for miRNA-based therapeutics are illustrated.

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The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune Checkpoint

Cited by 107 publications

References 67 publications

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2

microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics

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