PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs

Ashrafizadeh, Milad; Zarrabi, Ali; Hushmandi, Kiavash; Zarrin, Vahideh; Moghadam, Ebrahim Rahmani; Zabolian, Amirhossein; Tavakol, Shima; Samarghandian, Saeed; Najafi, Masoud

doi:10.1016/j.lfs.2020.117899

Cited by 54 publications

(32 citation statements)

References 204 publications

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“…miRNAs, a class of noncoding RNAs (ncRNAs) comprising 18–24 nucleotides, participate in tumor immune evasion by the transcriptional regulation of the PD‐L1/PD‐1 axis 99–101 . In human ovarian cancer Skov3 cells, miR‐424 decreased the PD‐L1 and CD80 levels by binding to the 3′‐untranslated region 100 .…”

Section: Role Of Hif‐1α In Tumor‐associated Antigen Presentationmentioning

confidence: 99%

The role of hypoxia‐inducible factor 1 in tumor immune evasion

Wang

et al. 2020

Medicinal Research Reviews

184

136

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Hypoxia‐inducible factor 1 (HIF‐1) plays an indispensable role in the hypoxic tumor microenvironment. Hypoxia and HIF‐1 are involved in multiple aspects of tumor progression, such as metastasis, angiogenesis, and immune evasion. In innate and adaptive immune systems, malignant tumor cells avoid their recognition and destruction by HIF‐1. Tumor immune evasion allows cancer cells to proliferate and metastasize and is associated with immunotherapy failure and chemoresistance. In the hypoxic tumor microenvironment, HIF‐1 signaling suppresses the innate and adaptive immune systems to evade immune attack by inducing the expression of immunosuppressive factors and immune checkpoint molecules, including vascular endothelial growth factor, prostaglandin E2, and programmed death‐ligand 1/programmed death‐1. Moreover, HIF‐1 blocks tumor‐associated antigen presentation via major histocompatibility complex class I chain‐related/natural killer group 2, member D signaling. Tumor‐associated autophagy and the release of tumor‐derived exosomes contribute to HIF‐1‐mediated immune evasion. This review focuses on recent findings on the potential mechanism(s) underlying the effect of hypoxia and HIF‐1 signaling on tumor immune evasion in the hypoxic tumor microenvironment. The effects of HIF‐1 on immune checkpoint molecules, immunosuppressive molecules, autophagy, and exosomes have been described. Additionally, the potential role of HIF‐1 in the regulation of tumor‐derived exosomes, as well as the roles of HIF‐1 and exosomes in tumor evasion, are discussed. This study will contribute to our understanding of HIF‐1‐mediated tumor immune evasion, leading to the development of effective HIF‐1‐targeting drugs and immunotherapies.

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Section: Role Of Hif‐1α In Tumor‐associated Antigen Presentationmentioning

confidence: 99%

The role of hypoxia‐inducible factor 1 in tumor immune evasion

Wang

et al. 2020

Medicinal Research Reviews

184

136

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“…sPD-L1 can arise from a non-proteolytic process, via an alternative splicing. The PD-L1 gene (and corresponding PD-L1 pre-mRNA) can generate many different splice variants, including a long non-coding RNA isoform (PD-L1-lnc) [ 100 , 101 ] and a variety of variants leading to truncated proteins. These isoforms have been shown to play distinct roles in the regulation of immune surveillance and progression in colorectal cancer [ 102 , 103 ].…”

Section: Generation Of Soluble Pd-l1: Proteolysis and Alternative Splicingmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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Upon T-cell receptor stimulation, the Programmed cell Death-1 receptor (PD-1) expressed on T-cells can interact with its ligand PD-L1 expressed at the surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 or PD-L1 are routinely used for the treatment of cancers, but their clinical efficacy varies largely across the variety of tumor types. A part of the variability is linked to the existence of several forms of PD-L1, either expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1). Here, we have reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein. sPD-L1 isoforms can be generated essentially by two non-exclusive processes: (i) proteolysis of m/exoPD-L1 by metalloproteases, such as metalloproteinases (MMP) and A disintegrin and metalloproteases (ADAM), which are capable of shedding membrane PD-L1 to release an active soluble form, and (ii) the alternative splicing of PD-L1 pre-mRNA, leading in some cases to the release of sPD-L1 protein isoforms lacking the transmembrane domain. The expression and secretion of sPD-L1 have been observed in a large variety of pathologies, well beyond cancer, notably in different pulmonary diseases, chronic inflammatory and autoimmune disorders, and viral diseases. The expression and role of sPD-L1 during pregnancy are also evoked. The structural heterogeneity of sPD-L1 proteins, and associated functional/cellular plurality, should be kept in mind when considering sPD-L1 as a biomarker or as a drug target. The membrane, exosomal and soluble forms of PD-L1 are all integral parts of the highly dynamic PD-1/PD-L1 signaling pathway, essential for immune-tolerance or immune-escape.

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“…Overexpression of NONHSAT141924 significantly lowers the survivability of MCF-7 cells by modulating the Bcl-2 apoptosis signaling pathway, suggesting a potential mechanism of resistance. Inhibition of NONHSAT141924 may be an effective strategy to treat PTX-resistant BCs ( [126] and reviewed in [127]).…”

Section: Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

Mechanisms of Taxane Resistance

Maloney

Hoover

Morejon-Lasso

et al. 2020

Cancers

121

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The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.

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PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs

Cited by 54 publications

References 204 publications

The role of hypoxia‐inducible factor 1 in tumor immune evasion

The role of hypoxia‐inducible factor 1 in tumor immune evasion

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Mechanisms of Taxane Resistance

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