Effect of laminin environments and tumor factors on the biology of myeloid dendritic cells

Phillippi, Ben; Singh, Manindra; Loftus, Tiffany; Smith, Hannah; Muccioli, Maria; Wright, Julia; Pate, Michelle; Benencia, Fabián

doi:10.1016/j.imbio.2019.10.003

Cited by 8 publications

(5 citation statements)

References 68 publications

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“…Furthermore, we also found that VM cells, who are mainly influencer and mediator, have extensive and unique interactions with immune cells in the microenvironment through the LAMININ pathway ( Supplementary Figures S5B–D ). There have been previous reports that laminin is involved in immunosuppression, which indicates that the LAMININ pathway may also be an important way for VM to promote or mediate the formation of a suppressed immune microenvironment ( Simon et al, 2019 ; Phillippi et al, 2020 ; Lepucki et al, 2022 ; Flies et al, 2023 ). Moreover, we further analyzed the correlation between VM and immune response steps in KIRC.…”

Section: Resultsmentioning

confidence: 99%

“…Our research also indicated that VM cells are a type of cell in TME with the highest expression of TGFβ and interact extensively with immune cells through the TGFβ signaling pathway. In addition, VM cells interact uniquely with immune cells through laminin, which has been reported to have both immune promotion and suppression properties ( Huard et al, 1985 ; Simon et al, 2019 ; Phillippi et al, 2020 ; Lepucki et al, 2022 ; Flies et al, 2023 ). We speculate that VM cells may mediate immune evasion by utilizing its immunosuppressive effect.…”

Section: Discussionmentioning

confidence: 99%

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Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

Tang,

Chen,

Liu

et al. 2024

Front. Pharmacol.

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Introduction:Vasculogenic mimicry (VM) represents a novel form of tumor angiogenesis that is associated with tumor invasiveness and drug resistance. However, the VM landscape across cancer types remains poorly understood. In this study, we elucidate the characterizations of VM across cancers based on multi-omics data and provide potential targeted therapeutic strategies.Methods:Multi-omics data from The Cancer Genome Atlas was used to conduct comprehensive analyses of the characteristics of VM related genes (VRGs) across cancer types. Pan-cancer vasculogenic mimicry score was established to provide a depiction of the VM landscape across cancer types. The correlation between VM and cancer phenotypes was conducted to explore potential regulatory mechanisms of VM. We further systematically examined the relationship between VM and both tumor immunity and tumor microenvironment (TME). In addition, cell communication analysis based on single-cell transcriptome data was used to investigate the interactions between VM cells and TME. Finally, transcriptional and drug response data from the Genomics of Drug Sensitivity in Cancer database were utilized to identify potential therapeutic targets and drugs. The impact of VM on immunotherapy was also further clarified.Results:Our study revealed that VRGs were dysregulated in tumor and regulated by multiple mechanisms. Then, VM level was found to be heterogeneous among different tumors and correlated with tumor invasiveness, metastatic potential, malignancy, and prognosis. VM was found to be strongly associated with epithelial-mesenchymal transition (EMT). Further analyses revealed cancer-associated fibroblasts can promote EMT and VM formation. Furthermore, the immune-suppressive state is associated with a microenvironment characterized by high levels of VM. VM score can be used as an indicator to predict the effect of immunotherapy. Finally, seven potential drugs targeting VM were identified.Conclusion:In conclusion, we elucidate the characteristics and key regulatory mechanisms of VM across various cancer types, underscoring the pivotal role of CAFs in VM. VM was further found to be associated with the immunosuppressive TME. We also provide clues for the research of drugs targeting VM. Our study provides an initial overview and reference point for future research on VM, opening up new avenues for therapeutic intervention.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

Tang,

Chen,

Liu

et al. 2024

Front. Pharmacol.

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“…Analysis of T-cell trajectories in tumors revealed that both CD4+ and CD8+ T-cells were trapped in fibronectin- and collagen-rich stromal regions, suggesting that the ECM may facilitate immune evasion by hindering proper infiltration of T-cells into tumors [ 66 ]. In addition, studies have speculated that laminin can induce a similar mechanism of dendritic cell tolerance and promote tumor immune escape [ 139 ]. Proteoglycan and Hyaluronic acid from ECM components can bind Toll-like receptors-2 and -4 to induce inflammatory gene expression, thereby exacerbating tumor-site inflammation [ 140 , 141 ].…”

Section: Ecm Pcscs and Metastasismentioning

confidence: 99%

The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC

Wang

et al. 2022

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. This pathological ECM promotes cancer growth, survival, invasion, and alters the behavior of fibroblasts and immune cells leading to metastasis formation and chemotherapy resistance, which contribute to the high lethality of PDAC. Additionally, recent evidence highlights that ECM, as a major structural component of the tumor microenvironment, is a highly dynamic structure in which ECM proteins establish a physical and biochemical niche for cancer stem cells (CSCs). CSCs are characterized by self-renewal, tumor initiation, and resistance to chemotherapeutics. In this review, we will discuss the effects of the ECM on tumor biological behavior and its molecular impact on the fundamental signaling pathways in PDAC. We will also provide an overview of how the different ECM components are able to modulate CSCs properties and finally discuss the current and ongoing therapeutic strategies targeting the ECM. Given the many challenges facing current targeted therapies for PDAC, a better understanding of molecular events involving the interplay of ECM and CSC will be key in identifying more effective therapeutic strategies to eliminate CSCs and ultimately to improve survival in patients that are suffering from this deadly disease.

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“…This process improved the synthesis of cholesterol and FAs in ovarian cancer cells (124). In addition, ovarian cancer cells are capable of producing several forms of laminins (125). The Akt and MEK signaling pathways are activated in DCs cultivated with laminins in vitro, and a shift in the metabolic state of DCs induces the development of their reprogramming from bone marrow precursors to a suppressive phenotype (125).…”

Section: Metabolic Signaling Pathways In Time Reprogrammingmentioning

confidence: 99%

Metabolic reprogramming of the tumor immune microenvironment in ovarian cancer: A novel orientation for immunotherapy

Lin

Zhou

et al. 2022

Front. Immunol.

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Ovarian cancer is the most lethal gynecologic tumor, with the highest mortality rate. Numerous studies have been conducted on the treatment of ovarian cancer in the hopes of improving therapeutic outcomes. Immune cells have been revealed to play a dual function in the development of ovarian cancer, acting as both tumor promoters and tumor suppressors. Increasingly, the tumor immune microenvironment (TIME) has been proposed and confirmed to play a unique role in tumor development and treatment by altering immunosuppressive and cytotoxic responses in the vicinity of tumor cells through metabolic reprogramming. Furthermore, studies of immunometabolism have provided new insights into the understanding of the TIME. Targeting or activating metabolic processes of the TIME has the potential to be an antitumor therapy modality. In this review, we summarize the composition of the TIME of ovarian cancer and its metabolic reprogramming, its relationship with drug resistance in ovarian cancer, and recent research advances in immunotherapy.

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Effect of laminin environments and tumor factors on the biology of myeloid dendritic cells

Cited by 8 publications

References 68 publications

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC

Metabolic reprogramming of the tumor immune microenvironment in ovarian cancer: A novel orientation for immunotherapy

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