MDK promotes M2 macrophage polarization to remodel the tumour microenvironment in clear cell renal cell carcinoma.

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Understanding the heterogeneity of the tumour microenvironment (TME) is crucial for developing advanced ccRCC therapies. Using publicly available ccRCC data (scRNA-seq, bulk RNA-seq, and somatic mutation data), a multiomics study was performed to explore TME heterogeneity. Three distinct ccRCC immune subtypes were identified through combined scRNA-seq and bulk RNA-seq analysis. A prognostic model based on unique cell signalling molecules in immunosuppressive tumour subtype was validated in the TCGA and CheckMate cohorts. MDK emerged as a critical regulatory gene in the immunosuppressive subtype, predicting a poor ccRCC prognosis and a poor immunotherapy response. MDK promotes M2 macrophage polarization via the MDK-LRP1 interaction, and the inhibition of MDK suppressed M2 polarization. This study revealed the heterogeneity of the ccRCC TME and a reliable prognostic model, shedding light on the vital role of MDK in the immunosuppressive TME and paving the way for optimized ccRCC immunotherapy.", "claims": [{"id": "claim-method", "statement": "Subsequently, via multivariate Cox regression analysis, we identified three independent prognostic factors: MDK, CD44, and COL6A2 (Fig. 6F).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39107475", "locator": "sections[30] \"Prognostic model construction and validation\" paragraph 2", "quote": "Subsequently, via multivariate Cox regression analysis, we identified three independent prognostic factors: MDK, CD44, and COL6A2 (Fig. 6F)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study are available in online repositories. 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