Abstract 1580: Distinct pathways of lytic and blastic bone metastases in prostate cancer patients

The most common metastatic lesions of prostate cancer are in the bone and can be classified into three distinct pathologic subtypes: lytic, blastic, and an indeterminate mixture of both. There is no immunotherapy guidance for treating patients based on lytic or blastic tumor induced bone disease. To identify distinct tumor and stroma in lytic and blastic prostate cancer bone metastases, we investigated a cohort of decalcified formalin-fixed and paraffin-embedded (FFPE) patient bone biopsy specimens that contained metastatic prostate cancer with lytic or blastic features. Tissue sections were utilized for immunohistochemistry (IHC) staining, isolation of RNA for gene expression, and Digital Spatial Profiling (DSP) of changes in both the tumor and microenvironment. A diverse set of unique immune cell populations and signaling pathways to both lytic and blastic types of prostate cancer metastases were present. High proportions of macrophages were present in lytic tumor induced bone disease, and T cells were present in lytic and blastic samples. In blastic lesions, immune cells were enriched for pSTAT3 and components of the JAK-STAT pathway. In lytic lesions, immune cells exhibited enhanced pAKT activity and components of the PI3K-AKT pathway. Expression of key immune checkpoint targets were identified in blastic prostate cancer, providing new therapeutic targets for patients with bone metastases. To further investigate which individual cells comprising the stroma and tumor have active JAK-STAT signaling, we performed fluorescent multiplex-IHC (mIHC). A tumor and myeloid panel of antibodies was used to identify on a single cell resolution which specific cell types are enriched for pSTAT3 in the tumor microenvironment. The identification of pAKT or pSTAT3 as promising therapeutic targets could be rationally employed to individual patients. The presence of macrophages and T cells in samples suggest that conventionally “cold” prostate cancer bone metastases warrant reappraisal as capable immunotherapy responders. Biopsies could guide selection of patients into appropriate therapeutic interventions based on protein levels and RNA expression of desired targets in metastatic disease. Citation Format: Claire L. Ihle, Meredith D. Provera, Desiree M. Straign, E. Erin Smith, Susan M. Edgerton, Adrie Van Bokhoven, M. Scott Lucia, Philip Owens. Distinct pathways of lytic and blastic bone metastases in prostate cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1580.