Preprocessed spatial transcriptomics data and analysis code for HMGA2 links morphological evolution and microenvironment dynamics to systemic therapy response in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) exhibits significant heterogeneity due to morphological changes and tumor microenvironment dynamics, influencing systemic therapy responses. This study investigates the role of HMGA2 in these processes and its clinical impact. As HMGA2 expression increases, tumor cells transition from a clear to eosinophilic cytoplasm, with eccentric nuclei and prominent nucleoli, leading to a loss of vascular architecture. HMGA2-high patients exhibit poor prognosis due to aggressive tumor morphology but respond better to combination immune checkpoint inhibitor (ICI) therapy than tyrosine kinase inhibitor monotherapy. This suggests that ICI therapy is particularly effective in these patients. Multi-omics analysis revealed an association between HMGA2 expression and the interaction of progenitor exhausted CD8⁺ T cells with conventional type 1 dendritic cells, potentially enhancing ICI therapeutic responses. These findings suggest that HMGA2 contributes to histologic progression and immune regulation, serving as a marker for systemic therapy response in ccRCC.