Abstract B051: Systemic proteomic remodeling following nephrectomy in renal cell carcinoma

Abstract Background: Renal cell carcinoma (RCC) exerts widespread systemic effects. However, how the removal of the primary tumor reshapes the circulating proteome remains poorly defined. Characterizing these changes may reveal biomarkers of immune recovery and mechanisms by which tumors disrupt systemic immune function. Methods: We profiled plasma from 16 patients with RCC collected before and after nephrectomy using the SomaLogic SOMAscan 11k assay v5.0, which quantifies 11,000 proteins. Data were z-score normalized and scaled in R. Differential abundance was analyzed using paired t-tests with false discovery rate (FDR) correction. Pathway enrichment analysis was evaluated using the GSEA. Protein-protein correlation networks were generated with igraph, and global topological parameters (node degree, edge strength, and network density) were compared between pre- and post-nephrectomy samples. Results: Nephrectomy induced broad systemic proteomic remodeling, with 1,737 proteins significantly altered (FDR < 0.05) and marked decreases in immune-suppressive pathways. Network analysis showed reductions in extreme protein–protein correlations, node degree, and interaction strength. These changes indicate alleviation of the polarized systemic proteomic state associated with RCC. Conclusions: Our findings demonstrate that RCC drives coordinated systemic proteomic dysregulation that is partially reversed after nephrectomy. The observed reduction in network extremes reflects a global rebalancing of circulating protein interactions, providing insight into how tumors perturb systemic physiology. Plasma proteomics and network metrics may offer sensitive indicators of systemic immune recovery and potential biomarkers of post-surgical immune restoration. Citation Format: Stephanie Schwartz, Julia Walker, Vivien Moritz, Soki Kashima, Adebowale Adeniran, Wei Shen Tan, Fed Ghali, Patrick Kenney, Michael Hurwitz, David Braun. Systemic proteomic remodeling following nephrectomy in renal cell carcinoma [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B051.