Spatial immune profiling of bone-metastatic castration-resistant prostate cancer reveals radium-223 immunomodulates the bone-tumor microenvironment

作者：Paul Gettys Corn, Guoyu Yu, Yibo Fan, Miao Zhang, Patricia Troncoso, Devaki Shilpa Surasi, Suyu Liu, Jaffer A. Ajani, Christopher J. Logothetis, Guocan Wang, Theocharis Panaretakis, Sue-Hwa Lin · 发表于：Prostate Cancer and Prostatic Diseases · 年份：2025 · DOI：10.1038/s41391-025-01069-1 · 被引用次数：2 · 研究领域：Prostate Cancer Treatment and Research、Radiopharmaceutical Chemistry and Applications、Cancer Immunotherapy and Biomarkers

Abstract Background Prostate cancer (PCa) bone lesions are bone-forming, which contribute to an immunosuppressive bone-tumor microenvironment (bone-TME). Targeting PCa-induced bone with the radiopharmaceutical Radium-223 (Ra223) is approved for men with bone-metastatic castration-resistant PCa (bmCRPC). We studied the effect of Ra223 on spatial localization of tumor and immune cells in bmCRPC tumor biopsies to gain insights into therapeutic immunomodulation of the bone-TME. Methods Transiliac bone marrow biopsies were performed at baseline and end of treatment (EOT) in 24 patients with bmCRPC treated with Ra223. In three patients with paired specimens containing tumor, multiplex immunofluorescence was performed with antibodies for a tumor cell marker (CK), T-cell markers (CD3, CD4, CD8, FOXP3, and granzyme B), macrophage markers (CD68 [total macrophages] and CD206 [M2-like macrophages]). Results In all three patients, we observed enrichment of CD68 + macrophages, around tumor-induced bone at baseline. CD3 staining revealed T cell depletion where tumor cells formed large sheets but not where tumor cells were scattered. The effects of Ra223 on tumor cells and T cell subsets were heterogeneous. In one patient, tumor cells were reduced, and CD3 + /CD8 + T cells were increased. In a second patient who evidenced osteolytic progression, tumor cells were increased while CD3 + /CD8 + T cells were decreased. In a third patient, there was high number of tumor cells at baseline that mode...