Abstract A035: Tumor PTEN-Loss is Associated with Club-Like Cells Phenotype and CD4 T-Cell Infiltration in High-Risk Localized Prostate Cancer

Abstract The mechanisms by which a small subset of high-risk localized prostate cance becomes immunogenic is not well understood. The objective of this study is to identify the tumor intrinsic and extrinsic mechanisms associated with immunogenicity in this population with the goal of harnessing this knowledge to further immunotherapy in PCa. Methods We performed Visium and Xenium spatial transcriptomic profiling on radical prostatectomy specimens from untreated, high-risk, localized prostate cancer patients obtained from the UCLA biobank with varying level of intra-tumoral T-cell infiltration (TILs). Validation was performed using OPAL multiplex immune-fluorescence (mxIF) staining for CD4, CD8A, CD68, PIGR (marker of club cells), and PSA on 18 specimens from a separate cohort of untreated, intermediate to high-risk localized prostate cancer. Summary Spatial transcriptomic analysis identified cells with club-like features to be associated with global T cell infiltration. Both benign epithelium and PCa can adopt the club-like features by the expression of PIGR protein. Benign glands with club-like features have reduced androgen receptor activity while club-like PCa are enriched with PTEN loss by IHC. Regardless of cell type, expression of PIGR leads to close contact of T cells and club-like cells. Xenium profiling revealed that most T cells are activated CD4+ stem T cells expressing TCF1 protein that are spatially enriched with myeloid dendritic cells and plasmacytoid dendritic cells. Conclusions We defined a subset of immunogenic localized prostate cancer that expresses PIGR either in benign or tumor epithelium. Epithelial expression of PIGR is associated with TILs, suggesting a non-canonical route for immune recruitment and activation. Citation Format: Anson Ku, Rong Rong Huang, Sumeyra Kartel, Xingyu Chen, Kayla Heyward, Ross Lake, Rosina Lis, Nikil Pramod, Shana Trostel, Anna Baj, Etyan Ruppin, Scott Wilkinson, John Fenimore, Huihui Ye, Adam Sowalsky. Tumor PTEN-Loss is Associated with Club-Like Cells Phenotype and CD4 T-Cell Infiltration in High-Risk Localized Prostate Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A035.