Abstract C146: Disparities in the tumor-immune microenvironment of primary prostate cancer tumors and lymph node metastases at single-cell spatial resolution

Abstract

Prostate cancer exhibits stark racial disparities with African-American (AA) men experiencing 1.8-fold higher incidence and 2.2-fold higher mortality than European-American (EA) men. Lymph node metastasis (LNM) represents a critical transition in which the tumor microenvironment (TME) undergoes profound remodeling, yet race-stratified characterization of this compartment remains largely unexplored. Prostate cancers are also characterized by an ‘immune-cold’ tumor-immune microenvironment (TIME), and clinical trials using checkpoint inhibitors have not shown significant benefit in prostate cancer patients. Here we have integrated single-cell 10X Flex RNA sequencing and VisiumHD spatial transcriptomics to characterize racial disparities in FGFR3 expression, immune checkpoint engagement, and myeloid/macrophage biology in prostate cancer LNM. We performed 10X Flex scRNAseq on 48 samples (36 primary tumors and 12 LNM) from 41 patients (21 AA and 20 EA) including 7 matched pairs of primary and LNM from the same patients (3 AA and 4 EA). We also performed VisiumHD spatial RNAseq profiling of 19 samples from 13 independent patients (5 AA, 7 EA, and 1 Asian) including 6 matched pairs of primary and LNM (2 AA, 3 EA, 1 Asian). RNA counts were quantified using CellRanger and SpaceRanger. Batch correction and sample integration were performed using Harmony in Seurat, and cell types were annotated using SingleR. Cell-cell communication via receptor-ligand interactions were computed using CellWhisper. We observed a fundamentally distinct metabolic program in AA tumors, with increased expression of oxidative phosphorylation (OXPHOS), MYC targets, mTORC1 signaling, adipogenesis, and fatty-acid metabolism gene sets. The GSEA analysis was consistent across epithelial, stromal, and immune compartments of the primary tumor, was reproducible across multiple analysis cohorts, and remained significant using three independent differential-expression methods after adjustment for grade, stage, mitochondrial content, and sequencing depth. Additionally, we observed that the interferon-γ (IFN-γ) response was highly enriched in AA tumors in the myeloid/stromal compartments. We also observed higher FGFR3 expression in AA primary tumors in both cohorts as well as in TCGA PRAD cases. Using within-patient paired analyses across races and tumor grade, we also observed increased FGF2-FGFR3 signaling in LNM relative to primary tumors based on spatial ligand-receptor co-expression using CellWhisper. Prostate tumors from AA men have distinct metabolic programs with strong increases in OXPHOS, adipogenesis, and fatty-acid metabolism pathways, as well as increased IFN-gamma signaling in myeloid and stromal cells. Jerry A. Ombor, Jatin Gandhi, Sergei Bombin, Brian G. Burns, Anurendra Kumar, Tilak B. Pathak, Cynthia L. Winham, Ismaheel O. Lawal, Olayinka A. Abiodun-Ojo, Rakesh Shiradkar, Lara Harik, Saurabh Sinha, Martin G. Sanda, David M. Schuster, Adeboye O. Osunkoya, Carlos S. Moreno. Disparities in the tumor-immune microenvironment of primary prostate cancer tumors and lymph node metastases at single-cell spatial resolution [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C146.