Abstract 6663: Integrated spatial transcriptomic and proteomic profiling reveals tumor-immune niches driving heterogeneity and resistance in clear cell renal cell carcinoma

Abstract Clear cell renal cell carcinoma (ccRCC) is a biologically heterogeneous malignancy shaped by complex tumor immune microenvironment interactions. Single-modality profiling often fails to capture this complexity. Spatial transcriptomics enables high-resolution mapping of gene expression, but proteins mediate functional states, signaling and therapeutic targets. Sequential integration of Imaging Mass Cytometry™ (IMC™) technology after spatial transcriptomics on the same tissue section adds a critical layer by quantifying protein expression and post-translational markers while preserving spatial context. Unlike fluorescence-based multiplexing, IMC technology avoids spectral overlap and autofluorescence, making it ideal for post-transcriptomic analysis. This multi-omic approach enables direct correlation of transcriptomic signatures with protein-level functional states, uncovering mechanisms of immune evasion and therapeutic resistance that remain hidden using transcriptomics alone. FFPE tumor sections from Stage 3 ccRCC patient were analyzed using spatial transcriptomics (Xenium 5K assay) followed by hematoxylin and eosin (H Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6663.