Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer

Zhang, Yijian; Zuo, Chunman; Liu, Liguo; Hu, Yunping; Yang, Bo; Qiu, Shimei; Yang, Li; Cao, Dongyan; Zheng, Jian; Ge, Junbo; Wang, Qiu; Wang, Ting; Bai, Lu; Yang, Yang; Li, Guoqiang; Shao, Ziyu; Gao, Yuan; Li, Yongsheng; Bian, Rui; Miao, Huijie; Li, Lin; Li, Xuechuan; Jiang, Chengkai; Yan, Siyuan; Wang, Ziyi; Wang, Zeyu; Cui, Xuya; Huang, Wen; Xiang, Dongxi; Wang, Congjun; Li, Qiyun; Wu, Xiangsong; Gong, Weiwei; Liu, Yun; Shao, Rong; Liu, Fatao; Li, Maolan; Chen, Luonan; Liu, Yingbin

doi:10.1016/j.jhep.2021.06.023

Cited by 104 publications

(60 citation statements)

References 42 publications

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“…Based on our results, MDK , which was secreted by GBM cancer cells, induced the migration and immunosuppressive polarization of macrophages. Our results were consistent with the role of MDK identified by Zhang et al in 2021 ( 41 ). In their gallbladder cancer research, MDK interacts with its receptor LRP1 , which is expressed by tumor-infiltrating macrophages, and further promotes immunosuppressive macrophage differentiation.…”

Section: Discussionsupporting

confidence: 94%

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses

et al. 2022

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PurposeGlioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N6-methyladenosine (m6A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m6A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level.Experimental DesignSingle-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m6A regulators and multiple factors.ResultsHNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m6A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m6A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m6A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m6A/high ICP and high m6A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance.ConclusionAt the single-cell level, m6A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m6A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.

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Section: Discussionsupporting

confidence: 94%

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses

et al. 2022

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“…The variability of tumor disease results from the initial genetic state of the tumor cells, their subsequent mutations, epithelialmesenchymal transition, and interactions with the innate immune system Longo (2011). Recently, in case of cancer the crosstalk of tumor cells with immune cells has been investigated in more detail Zhang et al (2021). In sepsis, the innate immune system is activated by infection and the clinical course is determined by the individual patient's initial condition.…”

Section: Introductionmentioning

confidence: 99%

Modeling Tumor Disease and Sepsis by Networks of Adaptively Coupled Phase Oscillators

Sawicki

Berner

Löser³

et al. 2022

Front. Netw. Physiol.

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In this study, we provide a dynamical systems perspective to the modelling of pathological states induced by tumors or infection. A unified disease model is established using the innate immune system as the reference point. We propose a two-layer network model for carcinogenesis and sepsis based upon the interaction of parenchymal cells and immune cells via cytokines, and the co-evolutionary dynamics of parenchymal, immune cells, and cytokines. Our aim is to show that the complex cellular cooperation between parenchyma and stroma (immune layer) in the physiological and pathological case can be qualitatively and functionally described by a simple paradigmatic model of phase oscillators. By this, we explain carcinogenesis, tumor progression, and sepsis by destabilization of the healthy homeostatic state (frequency synchronized), and emergence of a pathological state (desynchronized or multifrequency cluster). The coupled dynamics of parenchymal cells (metabolism) and nonspecific immune cells (reaction of innate immune system) are represented by nodes of a duplex layer. The cytokine interaction is modeled by adaptive coupling weights between the nodes representing the immune cells (with fast adaptation time scale) and the parenchymal cells (slow adaptation time scale) and between the pairs of parenchymal and immune cells in the duplex network (fixed bidirectional coupling). Thereby, carcinogenesis, organ dysfunction in sepsis, and recurrence risk can be described in a correct functional context.

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“…It was also identified to contribute to multidrug resistance in GC cells 81 . Besides, MDK rewires immunosuppressive environment in melanoma and gallbladder cancer 82 83 . In this study, we found that MDK is overexpressed in EGC and AG patients comparing with NAG ones.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

Gao

et al. 2022

Preprint

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While the changes of tumor immune microenvironment (TME) have critical implications for most tumor progression, works that could reveal the compositions and immunity features of TME are needed. Profiling gastric malignant cells at single-cells resolution has shown the transcriptional heterogeneity is represented at different states of gastric cancer, implying that diverse cell states may exist, including immune cells, and all components in TME make some balances in early gastric cancer (EGC) progression. However, it remains unclear how immune cells contributing malignancy of gastritis, constituting general characteristics of gastric TME. Furthermore, the role of specific interactions among cells in gastric TME remains to be illustrated. Here, we performed spatial transcriptomes and single-cell RNA-seq analysis across 18 gastric samples, identifying 17 celltypes and reconstructing their location information. We found that immune cells represented different degree of dysregulations during the progression from non-atrophic gastritis (NAG), atrophic gastritis (AG) to EGC, including imbalance of cytotoxic and inhibitory effects in T cells, maturation inhibition in B cells and malignant genes up-regulated obviously in myeloid cells. Besides, pathway activities showed that hypoxia, reactive oxygen species and fatty metabolism signaling were activated from AG stage, which may accelerate progression of EGC. Moreover, cellular interactions further identified the roles of hypoxia in gastric TME. Overall, the multi-omics data presented in this study offer a comprehensive view of immune cell types, states changes and locations within the gastric tissues during the progression from NAG, AG to EGC, advancing our understanding of the composition and immunity of different gastric states, offering diagnostic and preventive thoughts for EGC.

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Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer

Abstract: Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer,

Cited by 104 publications

References 42 publications

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses

Modeling Tumor Disease and Sepsis by Networks of Adaptively Coupled Phase Oscillators

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

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