ArticleEBioMedicine2024
Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 33 citations in OpenAlex.
- Integrated spatial and single-cell transcriptomics uncover IFI6⁺ regulatory T-cells and SPP1⁺ macrophages immunosuppressive niches in colorectal cancer.British journal of cancer · 2026Article
- Single-cell and spatial transcriptomic profiling identifies a fibroblast-like endothelial state and the MDK-NCL signaling axis in prostate cancer microenvironment remodeling.Translational oncology · 2026Article
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- GDF15 promotes 5-Fluorouracil and Oxaliplatin resistance by promoting stem cell-like phenotype in colorectal cancer.British journal of cancer · 2026Article
- Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models.Cell reports. Medicine · 2026Article
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- Differences in T-cell Densities and Neighborhood Patterns in Human Colorectal Adenomas and Sessile Serrated Lesions.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Identification of the novel therapeutic target gene SLC12A9, which determines the prognosis of patients with colorectal cancer.Surgery today · 2026Article
- Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- Article
- EGFR deletion in myeloid cells reprograms the immunosuppressive landscape of colorectal cancer.Cell death and differentiation · 2026Article
- Targeting VEGF signaling and stromal remodeling enhances chemoimmunotherapy efficacy in esophageal cancer.Journal for immunotherapy of cancer · 2026Article
- Myoferlin contributes to invasiveness of human T-cell leukemia virus type 1-infected T cells.Journal of virology · 2026Article
- Integrated single-cell and bulk transcriptomic analyses unveil a necroptosis-related prognostic model and its association with tumor microenvironment remodeling in gastric cancer.Discover oncology · 2026Article
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Targeting regulatory T cells in gastrointestinal cancers: current status and future perspectives.International journal of clinical oncology · 2026Review
- A multimodal approach integrating NK cell-associated gene signatures and pathomics to predict colon adenocarcinoma prognosis.Scientific reports · 2026Article
- MDK Activates the PI3K/AKT Axis to Induce AP2A1 Expression and Epithelial-Mesenchymal Transition in Colorectal Cancer.Cancers · 2026Article
- NMolecular medicine reports · 2026Article
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43 authors at 15 institutions in 1 country.
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Abstract
backgroundCell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival.
methodsWe performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients.
findingsCRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients.
interpretationMDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC.
fundingJapan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.
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