The role of extracellular vesicles and PD-L1 in glioblastoma-mediated immunosuppressive monocyte induction

Himes, Benjamin; Peterson, Timothy E.; Mooij, Tristan de; Garcia, Luz Milbeth Cumba; Jung, Mi‐Yeon; Uhm, Sarah; Yan, David Z.; Tyson, Jasmine; Jin-Lee, Helen J.; Parney, Daniel; Abukhadra, Yasmina; Gustafson, Michael P.; Dietz, Allan B.; Johnson, Aaron J.; Dong, Haidong; Maus, Rachel L.G.; Markovic, Svetomir N.; Lucien, Fabrice; Parney, Ian F.

doi:10.1093/neuonc/noaa029

Cited by 73 publications

(62 citation statements)

References 45 publications

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“…This contributes to the pre‐metastatic niche, paving the way for subsequent metastases. PD‐L1 expression by tumour‐derived EVs can inhibit CD8 T‐cell proliferation, cytokine production and cytotoxicity, 41 and in turn induce the proliferation of other immunosuppressive cell types, such as PD‐1 positive nonclassical monocytes (NCM) 42 …”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicle‐associated organotropic metastasis

Cheong

Xiang

et al. 2020

Cell Proliferation

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Metastasis refers to the progressive dissemination of primary tumour cells and their colonization of other tissues and is associated with most cancer‐related mortalities. The disproportional and systematic distribution pattern of distant metastasis in different cancers has been well documented, as is termed metastatic organotropism, a process orchestrated by a combination of anatomical, pathophysiological, genetic and biochemical factors. Extracellular vesicles (EVs), nanosized cell‐derived membrane‐bound particles known to mediate intercellular communication, are now considered crucial in organ‐specific metastasis. Here, we review and summarize recent findings regarding EV‐associated organotropic metastasis as well as some of the general mechanisms by which EVs contribute to this important process in cancer and provide a future perspective on this emerging topic. We highlight studies that demonstrate a role of tumour‐derived EVs in organotropic metastasis via pre‐metastatic niche modulation. The bioactive cargo carried by EVs is of diagnostic and prognostic values, and counteracting the functions of such EVs may be a novel therapeutic strategy targeting metastasis. Further investigations are warranted to better understand the functions and mechanisms of EVs in organotropic metastasis and accelerate the relevant clinical translation.

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Section: Introductionmentioning

confidence: 99%

Extracellular vesicle‐associated organotropic metastasis

Cheong

Xiang

et al. 2020

Cell Proliferation

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“…LGG is the main subtype of gliomas, which characterized with lower aggressiveness and well differentiation than GBM counterpart. A growing number of studies focus on the interplay between glioma and immunity, but most research attach great attentions to the GBM [24][25][26]. LGG seems to be ignored from the field of cancer immunotherapy due to its better prognosis than GBM.…”

Section: Discussionmentioning

confidence: 99%

Characterization of clinical significance of PD-1/PD-Ls expression and methylation in patients with low grade glioma

Mei

Cai

et al. 2020

Preprint

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Background: Immune checkpoints play crucial roles in immune escape of cancer cells. However, the exact prognostic values of expression and methylation of programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1) and PD-L2 in low-grade glioma (LGG) have not been defined yet. Methods:A total of 514 LGG samples from TCGA dataset containing both PD-1, PD-L1 and PD-L2 expression, DNA methylation, and survival data were enrolled into our study. The clinical significance of PD-1/PD-Ls expression and methylation inLGG were explored. Besides, the correlation between PD-1/PD-Ls expression and methylation with the infiltration levels of tumor-infiltrating immune cells (TIICs) was assessed. Moreover, GO enticement analysis of PD-1/PD-Ls co-expressed genes was performed as well. R 3.6.2 and GraphPad Prism 8 were applied as main tools for the statistical analysis and graphical exhibition.Results: PD-1/PD-Ls had distinct co-expression patterns in LGG tissues. The expression and methylation status of PD-1/PD-Ls seemed to be various in differentLGG subtypes. Besides, upregulated PD-1/PD-Ls expression and hypo-methylation of PD-1/PD-Ls were associated with worse survival in LGG patients. In addition, PD-1/PD-Ls expression was revealed to be positively associated with TIICs infiltration, while their methylation was negatively associated with TIICs infiltration.Moreover, the PD-1/PDLs correlated gene profiles screening and Gene Ontology (GO) enrichment analysis uncovered that PD-1/PDLs and their positively correlated gene mainly participated in immune response related biological processes. Conclusions:High expression and hypo-methylation of PD-1/PD-Ls significantly correlated with unfavorable survival in LGG patients, suggesting LGG patients may benefit from PD1/PD-Ls checkpoint inhibitors treatment.

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“…This effect was correlated to the increased amount of EVassociated miR-10a and miR-21 that was able to activate MDSCs functions by targeting RAR-related orphan receptor alpha (RORA) and PTEN [30]. Further, the same group identified also TEV-associated miR-29a and miR-92a as responsible for MDSCs increased proliferation, but only miR-92a as the mediator of immunosuppressive functions [31].Further, data published in a very recent study, show that MDSCs, induced by glioblastoma-EVs, inhibit T cell proliferation [32].…”

Section: Tevs and Myeloid-derived Suppressor Cellsmentioning

confidence: 93%

“…Interestingly, glioblastoma-derived EVs drive the formation of non-classical monocytes (NCMs), CD14+/PD-1+/CD16+/HLA-DR high [32], a specific immunosuppressive cell population widely described as anti-inflammatory [133,134]. In the same study, the authors reported that TEV-conditioned NCMs inhibit T cell proliferation and that the presence of PD-L1 in TEVs is responsible for this effect [32].…”

Section: Tevs As the Carriers Of Pd-l1mentioning

confidence: 97%

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

Raimondo

Pucci

Alessandro

et al. 2020

IJMS

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The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

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The role of extracellular vesicles and PD-L1 in glioblastoma-mediated immunosuppressive monocyte induction

Cited by 73 publications

References 45 publications

Extracellular vesicle‐associated organotropic metastasis

Extracellular vesicle‐associated organotropic metastasis

Characterization of clinical significance of PD-1/PD-Ls expression and methylation in patients with low grade glioma

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

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