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Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients.
J Immunother Cancer 2019; 7(1):293JI

Abstract

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.

Authors+Show Affiliations

Cancer Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. philip.owens@cuanschutz.edu. Research Service, Department of Veterans Affairs, Eastern Colorado Health Care System, Aurora, CO, 80045, USA. philip.owens@cuanschutz.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31703602

Citation

Ihle, Claire L., et al. "Distinct Tumor Microenvironments of Lytic and Blastic Bone Metastases in Prostate Cancer Patients." Journal for Immunotherapy of Cancer, vol. 7, no. 1, 2019, p. 293.
Ihle CL, Provera MD, Straign DM, et al. Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients. J Immunother Cancer. 2019;7(1):293.
Ihle, C. L., Provera, M. D., Straign, D. M., Smith, E. E., Edgerton, S. M., Van Bokhoven, A., ... Owens, P. (2019). Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients. Journal for Immunotherapy of Cancer, 7(1), p. 293. doi:10.1186/s40425-019-0753-3.
Ihle CL, et al. Distinct Tumor Microenvironments of Lytic and Blastic Bone Metastases in Prostate Cancer Patients. J Immunother Cancer. 2019 Nov 8;7(1):293. PubMed PMID: 31703602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients. AU - Ihle,Claire L, AU - Provera,Meredith D, AU - Straign,Desiree M, AU - Smith,E Erin, AU - Edgerton,Susan M, AU - Van Bokhoven,Adrie, AU - Lucia,M Scott, AU - Owens,Philip, Y1 - 2019/11/08/ PY - 2019/06/12/received PY - 2019/09/20/accepted PY - 2019/11/10/entrez PY - 2019/11/11/pubmed PY - 2019/11/11/medline KW - Bone metastases KW - Digital spatial profiling KW - Prostate KW - Tumor microenvironment SP - 293 EP - 293 JF - Journal for immunotherapy of cancer JO - J Immunother Cancer VL - 7 IS - 1 N2 - 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. SN - 2051-1426 UR - https://www.unboundmedicine.com/medline/citation/31703602/Distinct_tumor_microenvironments_of_lytic_and_blastic_bone_metastases_in_prostate_cancer_patients L2 - https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0753-3 DB - PRIME DP - Unbound Medicine ER -