Immunosuppressive role of SPP1-CD44 in the tumor microenvironment of intrahepatic cholangiocarcinoma assessed by single-cell RNA sequencing

Cheng, Mei‐Ling; Liang, Guodong; Yin, Zheng; Lin, Xiaona; Sun, Qinghua; Liu, Yang

doi:10.1007/s00432-022-04498-w

Cited by 27 publications

(27 citation statements)

References 53 publications

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“…Currently, how osteopontin encoded by SPP1 interacts with TME still remains debated. Although SPP1+ macrophages have been generally reported to build intercellular networking with fibroblasts in colorectal cancer and lung cancer,23 44 there were few studies suggesting that SPP1 highly expressed in macrophages binds to its receptor CD44 on activated T cells to suppress cytotoxicity of T cells in TME 45 46. Here, our analysis supported that macrophages through SPP1-CD44 axis could interact with diverse subpopulations of immune cells in LUAD TME, such as CD8+ T cells, monocytes and mast cells.…”

Section: Discussionsupporting

confidence: 71%

Single-cell RNA-sequencing uncovers the dynamic changes of tumour immune microenvironment in advanced lung adenocarcinoma

Lu,

Qian,

Cheng

et al. 2023

BMJ Open Resp Res

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BackgroundThe heterogeneity of lung adenocarcinoma (LUAD) plays a vital role in determining the development of cancer and therapeutic sensitivity and significantly hinders the clinical treatment of LUAD.ObjectiveTo elucidate the cellular composition and reveal previously uncharacterised tumour microenvironment in LUAD using single-cell RNA-sequencing (scRNA-seq).MethodsTwo scRNA-seq datasets with 106 829 high-quality cells from 34 patients including 11 normal, 9 early (stage I and II) and 14 advanced (stage III and IV) LUAD were integrated and clustered to explore diagnostic and therapeutic cell populations and their biomarkers for diverse stages of LUAD. Three independent bulk RNA-seq datasets were used to validate the results from scRNA-seq analysis. The expression of marker genes for specific cell types in early and advanced LUAD was verified by immunohistochemistry (IHC).ResultsComprehensive cluster analysis identified that S100P+ epithelial and SPP1+ macrophage, positively related to poor outcomes, were preferentially enriched in advanced stage. Although the accumulation of KLRB1+CD8+ T cell and IGHA1+/IGHG1+ plasma cell both significantly associated the favourable prognosis, we also found KLRB1+CD8+ T cell decreased in advanced stage while IGHA1+/IGHG1+ plasma cells were increased. Cell-cell communication analysis showed that SPP1+ macrophage could interact with most of CD8+ subclusters through SPP1-CD44 axis. Furthermore, based on three independent bulk RNA-seq datasets, we built risk model with nine marker genes for specific cell subtypes and conducted deconvolution analysis, both supporting our results from scRNA-seq data. We finally validated the expression of four marker genes in early and advanced LUAD by IHC.ConclusionOur analyses highlight the molecular dynamics of LUAD epithelial and microenvironment and provide new targets to improve LUAD therapy.

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Section: Discussionsupporting

confidence: 71%

Single-cell RNA-sequencing uncovers the dynamic changes of tumour immune microenvironment in advanced lung adenocarcinoma

Lu,

Qian,

Cheng

et al. 2023

BMJ Open Resp Res

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“…Studies have demonstrated that CD44 plays a critical role in the occurrence and progression of CCA. − It regulates various biological behaviors of tumor cells, including proliferation, migration, and invasion, and is involved in the formation and modulation of the tumor microenvironment. Hence, CD44 has emerged as a potential target for the diagnosis and treatment of CCA, and it can be utilized in research related to targeted therapy and immunotherapy . First, we measured the protein and mRNA expression levels of endogenous CD44 in CCA cell line QBC939 and the normal biliary epithelial cell line HIBEC (Figure A,B).…”

Section: Resultsmentioning

confidence: 99%

Targeted Delivery of Gemcitabine for Precision Therapy of Cholangiocarcinoma Using Hyaluronic Acid-Modified Metal–Organic Framework Nanoparticles

Long,

Peng,

Yang

et al. 2024

ACS Omega

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Chemotherapy is widely recognized as an important approach for the treatment of cholangiocarcinoma. Gemcitabine (GEM) has been considered a first-line drug for treating cholangiocarcinoma due to its ability to effectively inhibit the proliferation, migration, and invasion of liver cancer cells. However, the systemic toxicity, premature degradation, and lack of tumortargeting properties of GEM limit its application in cholangiocarcinoma chemotherapy. Additionally, precise targeted delivery of GEM is necessary to align with the current concept of precision medicine. In this study, considering the overexpression of hyaluronic acid (HA) receptors (CD44) on cholangiocarcinoma cells, we

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“…Importantly, we detected outgoing signals from keratinocytes to other cells associated with EGF and SPP1 signaling pathways. Ligand:receptor pairs in the infected niche ( Figure S2D ) included Hbegf:Egfr for the EGF pathway and Spp1:Cd44, Spp1:(Itga5+Itgb1), Spp1:(Itga9+Itgb1), and Spp1:(Itgav+Itgb3) for the SPP1 pathway ( Figures 2L , S2D , and S2E ), that are known to induce immunosuppression (Cheng et al, 2023; Gao et al, 2022). Remarkably, we observed the enrichment of keratinocyte-endothelial cell ligand:receptor pairs ( Figure S3 and Table S6 ).…”

Section: Resultsmentioning

confidence: 99%

Decoding the complexity of delayed wound healing followingEnterococcus faecalisinfection

Celik,

Lee,

Tanoto

et al. 2023

Preprint

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Wound infections are highly prevalent, and can lead to delayed or failed healing, causing significant morbidity and adverse economic impacts. These infections occur in various contexts, including diabetic foot ulcers, burns, and surgical sites.Enterococcus faecalisis often found in persistent non-healing wounds, but its contribution to chronic wounds remains understudied. To address this, we employed single-cell RNA sequencing (scRNA-seq) on infected wounds in comparison to uninfected wounds in a mouse model. Examining over 23,000 cells, we created a comprehensive single-cell atlas that captures the cellular and transcriptomic landscape of these wounds. Our analysis revealed unique transcriptional and metabolic alterations in infected wounds, elucidating the distinct molecular changes associated with bacterial infection compared to the normal wound healing process. We identified dysregulated keratinocyte and fibroblast transcriptomes in response to infection, jointly contributing to an anti-inflammatory environment. Notably,E. faecalisinfection prompted a premature, incomplete epithelial-to-mesenchymal transition in keratinocytes. Additionally,E. faecalisinfection modulated M2-like macrophage polarization by inhibiting pro-inflammatory resolutionin vitro,in vivo,and in our scRNA-seq atlas. Furthermore, we discovered macrophage crosstalk with neutrophils, which regulates chemokine signaling pathways, while promoting anti-inflammatory interactions with endothelial cells. Overall, our findings offer new insights into the immunosuppressive role ofE. faecalisin wound infections.AUTHOR SUMMARYWound infections, including diabetic foot ulcers, burns, or surgical sites, often lead to prolonged healing and significant health and economic burdens. Among the bacteria implicated in these persistent wounds,Enterococcus faecalisremains a relatively enigmatic player. To unravel its role in non-healing wounds, we used single-cell RNA sequencing in a mouse model, scrutinizing over 23,000 cells to construct a comprehensive single-cell map of infected wounds compared to uninfected wounds. Our investigation revealed distinct genetic and metabolic alterations in infected wounds, in which infection resulted in a perturbed inflammatory environment delayed wound healing signatures. Specifically,E. faecalisinfection induces a premature and incomplete transition in keratinocytes, impeding their healing function. Furthermore, infection influences the behavior of immune cells like macrophages, affecting the body’s response to the infection. These findings not only shed light onE. faecalis’s role in delayed wound healing but also offer potential avenues for future treatments, providing valuable insights into the challenging realm of wound infections.

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Immunosuppressive role of SPP1-CD44 in the tumor microenvironment of intrahepatic cholangiocarcinoma assessed by single-cell RNA sequencing

Cited by 27 publications

References 53 publications

Single-cell RNA-sequencing uncovers the dynamic changes of tumour immune microenvironment in advanced lung adenocarcinoma

Single-cell RNA-sequencing uncovers the dynamic changes of tumour immune microenvironment in advanced lung adenocarcinoma

Targeted Delivery of Gemcitabine for Precision Therapy of Cholangiocarcinoma Using Hyaluronic Acid-Modified Metal–Organic Framework Nanoparticles

Decoding the complexity of delayed wound healing followingEnterococcus faecalisinfection

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