Lessons learned from spatial transcriptomic analyses in clear-cell renal cell carcinoma

Abstract

Spatial transcriptomics has emerged as a powerful tool for discerning the heterogeneity of the tumour microenvironment across various cancers, including renal cell carcinoma (RCC). Spatial transcriptomics-based studies conducted in clear-cell RCC (the only RCC subtype studied using this technique to date) have given insights into spatial interactions within this disease. These insights include the role of epithelial-to-mesenchymal transitioning, revealing proximity-dependent interactions between tumour cells, fibroblasts, interleukin-2-expressing macrophages and hyalinized regions. Investigations into metabolic programmes have shown high transcriptional heterogeneity within tumours, with a tendency of increased metabolic activity towards the tumour centre. T cell infiltration has been shown to be independent of neoantigen burden, although T cell activity correlates with both metabolic states and various transcripts expressed by tumour cells, fibroblasts and monocytes. The role of tertiary lymphoid structures in both plasma cell maturation and their infiltration of the tumour has been shown through tracks of fibroblasts. Collectively, these findings indicate the potential of spatial transcriptomics to reveal predictive spatial features, supporting its promise in the development of biomarkers for clear-cell RCC management.