The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200

Noman, Muhammad Zaeem; Janji, Bassam; Abdou, Abdérémane; Hasmim, Meriem; Terry, Stéphane; Tan, Tuan Zea; Mami‐Chouaib, Fathia; Thiery, Jean Paul; Chouaı̈b, Salem

doi:10.1080/2162402x.2016.1263412

Cited by 219 publications

(195 citation statements)

References 20 publications

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“…(49) Similarly, Noman et al reported that the selective upregulation of PD-L1 was dependent on the ZEB1/miR-200 axis in breast cancer. (50) In this article, we designed our study focus based on the PD-L1 gene promoter region containing a binding site for ZEB1. No report has previously investigated the PD-L1 gene promoter region for ZEB1 binding so far.…”

Section: Discussionmentioning

confidence: 99%

Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma

et al. 2017

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Programmed death‐ligand 1 (PD‐L1) plays a crucial role in the host immune system in cancer progression. The gene promoter region of PD‐L1 also contains a binding site for ZEB1, a transcription factor related to epithelial‐mesenchymal transition (EMT). The purpose of this study was to clarify the relationship between PD‐L1 and EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). PD‐L1 and ZEB1 expression at the tumor invasive front was examined by immunohistochemistry in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy, and their expression and clinicopathological factors were compared. ZEB1 and PD‐L1 expression was determined in TE8 cells, which demonstrate the EMT phenotype, following ZEB1 knockdown by siZEB1. TE5, TE6 and TE11 cells with non‐EMT phenotype were also used for studies of TGF‐β1‐dependent EMT induction and ZEB1 and PD‐L1 expression. In cases of high PD‐L1 expression at the invasive front, significantly greater depth of tumor invasion, EMT, and less CD8+ lymphocyte infiltration were observed. High PD‐L1 expression was also associated with worse overall and relapse‐free survival. A correlation was observed between PD‐L1 and ZEB1 expression. In TE8 cells, siZEB1 suppressed PD‐L1 and promoted E‐cadherin mRNA and protein expression. TGF‐β1 induced EMT and surface expression of PD‐L1 in TE5, TE6 and TE11 cell lines. PD‐L1 expression at the ESCC invasive front was related to ZEB1 expression, EMT and poor prognosis. We suggest that a cooperative mechanism bridging between tumor immune avoidance and EMT contributes to tumor malignancy in ESCC.

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Section: Discussionmentioning

confidence: 99%

Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma

et al. 2017

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“…). In this regard, we recently investigated the expression levels of PD‐L1 in the Mes MCF7 derivatives (Noman et al ., ). While PD‐L1 was highly expressed in MCF7 cells silenced for WISP2, other cell lines had little or no expression of PD‐L1 similar to that found in the parental MCF7 cells.…”

Section: The Acquisition Of a Mesenchymal Phenotype Is Associated Witmentioning

confidence: 97%

New insights into the role of EMT in tumor immune escape

et al. 2017

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Novel immunotherapy approaches have provided durable remission in a significant number of cancer patients with cancers previously considered rapidly lethal. Nonetheless, the high degree of nonresponders, and in some cases the emergence of resistance in patients who do initially respond, represents a significant challenge in the field of cancer immunotherapy. These issues prompt much more extensive studies to better understand how cancer cells escape immune surveillance and resist immune attacks. Here, we review the current knowledge of how cellular heterogeneity and plasticity could be involved in shaping the tumor microenvironment (TME) and in controlling antitumor immunity. Indeed, recent findings have led to increased interest in the mechanisms by which cancer cells undergoing epithelial‐mesenchymal transition (EMT), or oscillating within the EMT spectrum, might contribute to immune escape through multiple routes. This includes shaping of the TME and decreased susceptibility to immune effector cells. Although much remains to be learned on the mechanisms at play, cancer cell clones with mesenchymal features emerging from the TME seem to be primed to face immune attacks by specialized killer cells of the immune system, the natural killer cells, and the cytotoxic T lymphocytes. Recent studies investigating patient tumors have suggested EMT as a candidate predictive marker to be explored for immunotherapy outcome. Promising data also exist on the potential utility of targeting these cancer cell populations to at least partly overcome such resistance. Research is now underway which may lead to considerable progress in optimization of treatments.

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“…This has been recently confirmed in human cancer. Breast cancer cells undergoing EMT indeed express PD-L1 in a miR-200-and ZEB1-dependent fashion (Noman et al, 2017).…”

Section: Emt and Adaptive Immune Cellsmentioning

confidence: 99%

“…The acquisition of EMT-like changes in tumor cells has been extensively studied and implies increased invasive properties, resistance to DNA damage-and chemotherapy-induced apoptosis, immunosuppression, and the acquisition of stem-like features. EMT transcriptomic signatures are found highly associated with groups of patients with poorer outcome in multiple cancer entities including breast cancer (Jang et al, 2015), colorectal cancer (Roepman et al, 2014), head and neck cancer (Pan et al, 2016), or malignant pleural mesothelioma (de Reynies et al, 2014). EMT-associated signaling pathways have lately been considered as therapeutic targets, as recently shown in a murine pancreatic cancer model (Subramani et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

EMT and inflammation: inseparable actors of cancer progression

et al. 2017

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Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor‐associated chronic inflammation is a hallmark of cancer that fosters progression to a metastatic stage, as has been extensively reviewed lately. Indeed, inflammatory cells persisting in the tumor establish a cross‐talk with tumor cells that may result in a phenotype switch into tumor‐supporting cells. This has been particularly well described for macrophages and is referred to as tumor‐associated ‘M2’ polarization. Epithelial‐to‐mesenchymal transition (EMT), the embryonic program that loosens cell–cell adherence complexes and endows cells with enhanced migratory and invasive properties, can be co‐opted by cancer cells during metastatic progression. Cancer cells that have undergone EMT are more aggressive, displaying increased invasiveness, stem‐like features, and resistance to apoptosis. EMT programs can also stimulate the production of proinflammatory factors by cancer cells. Conversely, inflammation is a potent inducer of EMT in tumors. Therefore, the two phenomena may sustain each other, in an alliance for metastasis. This is the focus of this review, where the interconnections between EMT programs and cellular and molecular actors of inflammation are described. We also recapitulate data linking the EMT/inflammation axis to metastasis.

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The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200

Cited by 219 publications

References 20 publications

Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma

Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma

New insights into the role of EMT in tumor immune escape

EMT and inflammation: inseparable actors of cancer progression

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