PMID- 31703602 OWN - NLM STAT- MEDLINE VI - 7 IP - 1 TI - Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients. PG - 293 LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 IS - 2051-1426 (Electronic) LID - 10.1186/s40425-019-0753-3 [doi] FAU - Ihle, Claire L AU - Ihle CL AD - Cancer Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Provera, Meredith D AU - Provera MD AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Straign, Desiree M AU - Straign DM AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Smith, E Erin AU - Smith EE AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Edgerton, Susan M AU - Edgerton SM AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Van Bokhoven, Adrie AU - Van Bokhoven A AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Lucia, M Scott AU - Lucia MS AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. FAU - Owens, Philip AU - Owens P AUID- ORCID: 0000-0002-1452-9285 AD - Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. philip.owens@cuanschutz.edu. AD - Research Service, Department of Veterans Affairs, Eastern Colorado Health Care System, Aurora, CO, 80045, USA. philip.owens@cuanschutz.edu. IS - 2051-1426 (Linking) RN - 0 (Biomarkers) SB - IM MH - Biomarkers MH - Bone Neoplasms/*diagnosis/*secondary MH - Computational Biology/methods MH - Gene Expression Profiling MH - Humans MH - Immunohistochemistry MH - Male MH - Prostatic Neoplasms/etiology/metabolism/*pathology MH - Signal Transduction MH - *Tumor Microenvironment OTO - NOTNLM OT - *Bone metastases OT - *Digital spatial profiling OT - *Prostate OT - *Tumor microenvironment PMC - PMC6839115 DCOM- 20200713 LR - 20200713 DP - 20191108 DEP - 20191108 AB - The most common metastatic lesions of prostate cancer are in bone and can be classified into three distinct pathology subtypes: lytic, blastic, and an indeterminate mixture of both. We investigated a cohort of decalcified formalin-fixed and paraffin-embedded (FFPE) patient specimens from the bone that contained metastatic prostate cancer with lytic or blastic features. These 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. In blastic lesions immune cells were enriched for pSTAT3 and components of the JAK-STAT pathway. In lytic-type lesions, immune cells were enriched for pAKT activity and components of the PI3K-AKT pathway. Enrichment for immune checkpoints including PD-L1, B7-H4, OX40L, and IDO-1 were identified in blastic prostate cancer, providing new therapeutic targets for patients with bone metastases. Biopsies could guide selection of patients into appropriate therapeutic interventions based on protein levels and RNA expression of desired targets in metastatic disease. Molecular pathology has been an excellent complement to the diagnosis, treatment, and management of primary tumors and could be successfully extended to patients with metastatic lesions.