Abstract B020: Survivin regulates tumorigenesis and immunogenicity of ccRCC

Abstract Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of renal cell carcinoma. TCGA analysis shows that high expression of the inhibitor of apoptosis protein survivin (BIRC5) correlates with advanced stage and poor prognosis. Recent work in our lab demonstrated that survivin promotes proliferation, migration, and mitochondrial remodeling in the RENCA RCC cell model, suggesting that survivin lies at the intersection of cell cycle and metabolic control. Preliminary RNA-seq analysis of survivin siRNA-treated RENCA cells indicated that immune-recruiting cytokines are upregulated upon survivin loss, which we validated in vitro. Because RENCA does not fully recapitulate ccRCC biology, we investigated how survivin loss influences mitochondrial homeostasis and the tumor–immune interface across VHL-deficient ccRCC models. We utilized a novel murine VHL-null ccRCC line (LVRCC), the VHL-proficient RENCA line, and the human VHL-deficient 786-O ccRCC line. Survivin was depleted by siRNA, followed by assessment of mitochondrial mass and immune cell recruitment using transwell co-culture assays. Notably, survivin knockdown in LVRCC cells produced a change in mitochondrial mass opposite to that observed in RENCA, a finding potentially related to VHL status. The VHL-deficient 786-O line exhibited phenotypes similar to LVRCC cells, including survivin-dependent growth. Survivin loss increased immune cell migration toward ccRCC cells, indicating that survivin restrains immune cell infiltration into the tumor microenvironment. Collectively, these data support survivin as an oncogenic driver and putative therapeutic target in ccRCC. Citation Format: Shivani S. Tuli, Yamato Murakami, Cais Vo, Yongho Bae, David Gau. Survivin regulates tumorigenesis and immunogenicity of ccRCC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr B020.