biostudies-literatureUnknown22(4)Chen JWThe progression and therapeutic response of clear cell renal cell carcinoma (ccRCC) are critically shaped by the complex interactions between tumor cell heterogeneity and the tumor immune microenvironment (TIME). However, a comprehensive classification of the ccRCC ecosystem and its clinical relevance is lacking. To address this, we utilized comprehensive bioinformatics approaches to analyze ten public single-cell RNA sequencing datasets from 194 samples across 118 ccRCC patients. Across 1,172,154 cells, we identified four TIME subtypes (immune activation, innate immunity, immunosuppressive myeloid [ISM], and immune exclusion) and six functional states of tumor cells (metabolic, angiogenic, stress-responsive, antigen-presenting, cell cycling, and epithelial-mesenchymal transition [EMT]). TInternational journal of biological sciences1807-1833https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905587biostudies-literatureFKBP10 promotes M2 polarization of macrophage via MEK/ERK/CXCL8 axis and facilitates tumor progression in clear cell renal cell carcinoma.PMC12905587Fu LMChen JWDeng QLuo JHLi JYWang YHWang JYLin HSZhou XWLiang HWei JHFeng HQLiu KZChen YHGui CPWang ZJin MYfalseFKBP10 promotes M2 polarization of macrophage via MEK/ERK/CXCL8 axis and facilitates tumor progression in clear cell renal cell carcinoma.The progression and therapeutic response of clear cell renal cell carcinoma (ccRCC) are critically shaped by the complex interactions between tumor cell heterogeneity and the tumor immune microenvironment (TIME). However, a comprehensive classification of the ccRCC ecosystem and its clinical relevance is lacking. To address this, we utilized comprehensive bioinformatics approaches to analyze ten public single-cell RNA sequencing datasets from 194 samples across 118 ccRCC patients. Across 1,172,154 cells, we identified four TIME subtypes (immune activation, innate immunity, immunosuppressive myeloid [ISM], and immune exclusion) and six functional states of tumor cells (metabolic, angiogenic, stress-responsive, antigen-presenting, cell cycling, and epithelial-mesenchymal transition [EMT]). T2026-01-01T00:00:00Z20262026-07-15T21:33:54.66Z2026-07-09T10:13:36.856ZS-EPMC129055874169457510.7150/ijbs.117535