The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia

Ding, Xiang; Wang, Liangliang; Zhang, Xuedong; Xu, Jianguang; Li, Peifeng; Liang, Hua; Zhang, Xianbin; Xie, Li; Zhou, Zihan; Yang, Jia; Weichselbaum, Ralph R.; Yu, Jinming; Hu, Man

doi:10.1186/s13045-021-01102-5

Cited by 95 publications

(69 citation statements)

References 9 publications

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“…HIF-1 and, more importantly, HIF-2 are required for the maintenance of cancer stem cells (CSCs) that are capable of self-renewal, and for generating both CSCs and differentiated cells [63]. HIF-1 promotes the CSC phenotype, enhancing the expression of KLF4, MYC, OCT4, SOX2, and NANOG [64][65][66][67]. Glioblastoma stem cells (GSC) are also favored by the stabilization of the Notch intracellular domain by HIF-1α.…”

Section: Hif-1α Promotes Gb Aggressivenessmentioning

confidence: 99%

Hypoxia: The Cornerstone of Glioblastoma

Doménech

Hernández

Plaja

et al. 2021

IJMS

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Glioblastoma is the most aggressive form of brain tumor in adults and is characterized by the presence of hypervascularization and necrosis, both caused by a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), the main factor activated by hypoxia, is an important driver of tumor progression in GB patients. HIF-1α is a transcription factor regulated by the presence or absence of O2. The expression of HIF-1 has been related to high-grade gliomas and aggressive tumor behavior. HIF-1 promotes tumor progression via the activation of angiogenesis, immunosuppression, and metabolic reprogramming, promoting cell invasion and survival. Moreover, in GB, HIF-1 is not solely modulated by oxygen but also by oncogenic signaling pathways, such as MAPK/ERK, p53, and PI3K/PTEN. Therefore, the inhibition of the hypoxia pathway could represent an important treatment alternative in a disease with very few therapy options. Here, we review the roles of HIF-1 in GB progression and the inhibitors that have been studied thus far, with the aim of shedding light on this devastating disease.

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Section: Hif-1α Promotes Gb Aggressivenessmentioning

confidence: 99%

Hypoxia: The Cornerstone of Glioblastoma

Doménech

Hernández

Plaja

et al. 2021

IJMS

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“…In parallel, the VEGF signaling is closely connected with hypoxia and the expression of HIF1A, and the significant upregulation of the HIF1A gene during storage may explain the increase in VEGF-A secretion [54]. Interestingly, the expression of PDL1 involved in the immunomodulatory activity of MSCs was significantly upregulated after storage, and the PDL1 expression can also be associated with the increased expression of HIF1A [55]. Conversely, the level of IL-6 in the conditioned medium decreased significantly after storage, which was accompanied by downregulation of the IL6 gene (Figures 3 and 4).…”

Section: Discussionmentioning

confidence: 98%

Hypothermic Storage of 3D Cultured Multipotent Mesenchymal Stromal Cells for Regenerative Medicine Applications

et al. 2022

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The regulatory requirements in cell processing, in the choice of a biomaterial scaffold and in quality control analysis, have to be followed in the clinical application of tissue-engineered grafts. Confirmation of sterility during quality control studies requires prolonged storage of the cell-based construct. After storage, preservation of the functional properties of the cells is an important prerequisite if the cells are to be used for cell-based tissue therapies. The study presented here shows the generation of 3D constructs based on Wharton’s jelly multipotent mesenchymal stromal cells (WJ-MSCs) and the clinically-acceptable HyaloFast® scaffold, and the effect of two- and six-day hypothermic storage of 3D cell-based constructs on the functional properties of populated cells. To study the viability, growth, gene expression, and paracrine secretion of WJ-MSCs within the scaffolds before and after storage, xeno-free culture conditions, metabolic, qPCR, and multiplex assays were applied. The WJ-MSCs adhered and proliferated within the 3D HyaloFast®. Our results show different viability of the cells after the 3D constructs have been stored under mild (25 °C) or strong (4 °C) hypothermia. At 4 °C, the significant decrease of metabolic activity of WJ-MSCs was detected after 2 days of storage, with almost complete cell loss after 6 days. In mild hypothermia (25 °C) the decrease in metabolic activity was less remarkable, confirming the suitability of these conditions for cell preservation in 3D environment. The significant changes were detected in gene expression and in the paracrine secretion profile after 2 and 6 days of storage at 25 °C. The results presented in this study are important for the rapid transfer of tissue engineering approaches into clinical applications.

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“…By preventing T-cell infiltration, the growth and invasiveness of GBM are supported [35]. As researched by Ding et al, in glioma cell lines, hypoxia upregulates PD-L1 expression via HIF-1α [36]. This is due to Semaphorin3A present on their surface that binds to its receptor on the BBB, the neu-ropilin1.…”

Section: Extracellular Vesicles-carriers Passing Through the Blood-br...mentioning

confidence: 97%

Section: Interactions Between Glioblastoma Cells and Tumor Microenvir...mentioning

confidence: 99%

Glioblastoma Microenvironment and Cellular Interactions

Crivii

Boșca

Melincovici

et al. 2022

Cancers

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The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell–cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.

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The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia

Cited by 95 publications

References 9 publications

Hypoxia: The Cornerstone of Glioblastoma

Hypoxia: The Cornerstone of Glioblastoma

Hypothermic Storage of 3D Cultured Multipotent Mesenchymal Stromal Cells for Regenerative Medicine Applications

Glioblastoma Microenvironment and Cellular Interactions

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