Abstract B035: Spatial multi-omic profiling of sarcomatoid and rhabdoid renal cell carcinoma reveals spatially distinct immune and tumor cell populations

Abstract Background: Rhabdoid and sarcomatoid (S/R) renal cell carcinoma (RCC) is a form of dedifferentiated RCC that can arise in the background of any RCC subtype. S/R features are associated with a more aggressive tumor phenotype and worse patient prognosis. Paradoxically, tumors with S/R differentiation demonstrate heightened sensitivity to immune checkpoint inhibitors (ICI) compared with their non-S/R counterparts. The mechanisms that drive this aggressive tumor phenotype and paradoxical ICIs sensitivity remain unclear. Prior studies have shown minimal genetic differences between S/R and non-S/R RCC, suggesting that non-genetic mechanisms drive this phenotype. Spatial multi-omic approaches are uniquely positioned to dissect the cellular and microenvironmental programs underlying S/R biology. Using a cohort of seven treatment-naïve patients with clear cell RCC (ccRCC) with S/R features, we performed spatial multi-omic characterization of tumor regions with sarcomatoid, rhabdoid, and/or ccRCC histology captured on the same tissue sections. Methods: Hematoxylin and eosin (H 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (5Suppl₂): Abstract nr B035.