Oncotarget

Research Papers:

Immune profiling of the bone marrow microenvironment in patients with high-risk localized prostate cancer

Erika Heninger, Nan Sethakorn, David Kosoff, Peiman Hematti, Morgan D. Kuczler, Kenneth J. Pienta and Joshua M. Lang _

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Oncotarget. 2020; 11:4253-4265. https://doi.org/10.18632/oncotarget.27817

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Abstract

Erika Heninger1, Nan Sethakorn2, David Kosoff3, Peiman Hematti1,3, Morgan D. Kuczler5, Kenneth J. Pienta4,5,6 and Joshua M. Lang1,3

1 University of Wisconsin Carbone Cancer Center, Madison, WI, USA

2 Department of Oncology, University of Wisconsin, Madison, WI, USA

3 Department of Medicine, University of Wisconsin, Madison, WI, USA

4 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, MD, USA

5 Department of Urology, The James Buchanan Brady Urological Institute, Baltimore, MD, USA

6 Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD, USA

Correspondence to:

Joshua M. Lang,email: jmlang@medicine.wisc.edu

Keywords: prostate cancer; bone marrow; tumor microenvironment; immune profiling; immune landscape

Received: July 28, 2020     Accepted: October 29, 2020     Published: November 17, 2020

Copyright: © 2020 Heninger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.


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