@article{291d82bc7ab64632b1f13edd2c3abf92,
title = "Immune profiling of the bone marrow microenvironment in patients with high-risk localized prostate cancer",
abstract = "Bone marrow (BM) is a primary metastatic site in prostate cancer (PC) and bone invasion is considered incurable. T cell-mediated immune surveillance is essential in controlling both tumorigenesis and initiation of metastases. Beside tropism, dissemination of PC cells to the BM may be facilitated by defects in BM immune homeostasis predisposing this niche to colonization. To evaluate the BM immune microenvironment in locally advanced, non-metastatic PC, we performed flow cytometry analysis of myeloid and lymphoid subsets in BM aspirates and peripheral blood collected during prostatectomy. Healthy BM aspirates served to establish a reference range for comparison. We found alterations in BM immune composition of PC patients, including an increased CD4/CD8 ratio, enrichment of CD4+ T cells, increased CD56+CD3+ NKT and CD56+CD3- NK yields compared to healthy controls. The lymphoid phenotype remained comparable regarding T cell activation and chemokine receptor-based polarization patterns. Additionally, we found increased B7H3 expression in the myeloid monocyte/ macrophage subset and decreased DC infiltration in BM of PC patients. These findings suggest that alterations in the immune milieu may limit immune surveillance that compromise the ability of the BM microenvironment to prevent tumor dissemination, and predispose development of bone metastases in a subset of patients with localized PC.",
keywords = "Bone marrow, Immune landscape, Immune profiling, Prostate cancer, Tumor microenvironment",
author = "Erika Heninger and Nan Sethakorn and David Kosoff and Peiman Hematti and Kuczler, {Morgan D.} and Pienta, {Kenneth J.} and Lang, {Joshua M.}",
note = "Funding Information: This work was supported by the 16CHAL04 Movember Foundation and Prostate Cancer Foundation Challenge Award, awarded to JML. This work was supported by the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program, Award No. W81XWH-16-1-0511 to JML and W81XWH-18-1-0273 to DK. NS was supported as a research fellow through the Advanced Fellowship in Women{\textquoteright}s Health/Department of Geriatrics at the William S. Middleton Veterans Affairs Hospital, Madison, WI, and is currently supported by a UW NRSA T32 post-doctoral award (5T32HL007899-23). Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. Additionally, we acknowledge shared resources grant support for the University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520 by the NIH for both the UWCCC Flow Cytometry Lab and Biostatistics Shared Resource at UWCCC. Funding Information: We are grateful for the support of patients who donated samples for this study. We thankfully acknowledge the technical assistance of Dr Anupama Singh and Serena Wolfe in processing samples and Dr Jamie Sperger for her support in writing of the manuscript. This work was supported by the 16CHAL04 Movember Foundation and Prostate Cancer Foundation Challenge Award, awarded to JML. This work was supported by the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program, Award No. W81XWH-16-1-0511 to JML and W81XWH-18-1-0273 to DK. NS was supported as a research fellow through the Advanced Fellowship in Women?s Health/Department of Geriatrics at the William S. Middleton Veterans Affairs Hospital, Madison, WI, and is currently supported by a UW NRSA T32 post-doctoral award (5T32HL007899-23). Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. Additionally, we acknowledge shared resources grant support for the University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520 by the NIH for both the UWCCC Flow Cytometry Lab and Biostatistics Shared Resource at UWCCC. Publisher Copyright: {\textcopyright} 2020 Heninger et al.",
year = "2020",
month = nov,
doi = "10.18632/ONCOTARGET.27817",
language = "English (US)",
volume = "11",
pages = "4253--4265",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "46",
}