Mapping therapy-responsive immune ecotypes in clear cell renal cell carcinoma through integrative omics

15 Jul 20264 min read0 viewsJournal Feed

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Clear cell renal cell carcinoma (ccRCC) is a kidney cancer in which immune activity is closely intertwined with von Hippel-Lindau (VHL) loss, hypoxia-inducible factor (HIF) signaling, angiogenesis, hypoxia, and metabolic adaptation. Although immune checkpoint inhibitor (ICI)-based regimens have changed the treatment landscape of advanced ccRCC, only a subset of patients achieve durable benefit.
Commonly used biomarkers, such as programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), and broad inflammatory gene signatures, have not been sufficient to explain this variation or to guide routine treatment selection. One reason is that immune infiltration in ccRCC is not synonymous with effective antitumor immunity.
A tumor rich in CD8+ T cells may still be resistant if these cells are exhausted, metabolically restricted, spatially separated from tumor nests, or surrounded by suppressive myeloid, stromal, and vascular programs. Therefore, the key issue is not simply whether a tumor is immunologically “hot” or “cold,” but which part of the antitumor response has failed.
In this Mini Review, we discuss ccRCC immunotherapy response from an immune-ecological perspective.

Frontiers in Immunology published a clinical update in Infectious Disease on 15 Jul 2026.

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Frontiers in Immunology