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Pericyte–stem Cell Crosstalk In CcRCC – Nature Reviews Nephrology –

The cells that surround tumours can influence tumour growth and response to therapy. In new research, ChuanJie Zhang and colleagues report the identification of a subset of pericytes that sustain the proliferation of cancer stem cells (CSCs) in clear cell renal cell carcinoma (ccRCC) and promote tumour resistance to tyrosine kinase inhibitors (TKIs).

PDGFRβ+GPR91+ pericytes, identified by single-cell RNA sequencing, were significantly enriched in ccRCC tumours compared to their levels in non-malignant adjacent kidney tissue. Moreover, PDGFRβ+GPR91+ frequency was associated with poorer outcomes and reduced sensitivity to TKI therapy. These findings were confirmed in mouse models of ccRCC, demonstrating that PDGFRβ+GPR91+ pericytes support tumour growth through the maintenance of CSCs, are themselves resistant to TKIs and also render tumours resistant to TKIs.