Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.

Classic Hodgkin lymphoma (CHL) characteristically shows few malignant cells in a microenvironment comprised of mixed inflammatory cells. Although CHL is associated with a high cure rate, recent studies have associated poor prognosis with absolute monocyte count in peripheral blood and increased mono...

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Main Authors: Ginell R Post, Youzhong Yuan, Emily R Holthoff, Charles M Quick, Steven R Post
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0224621
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author Ginell R Post
Youzhong Yuan
Emily R Holthoff
Charles M Quick
Steven R Post
author_facet Ginell R Post
Youzhong Yuan
Emily R Holthoff
Charles M Quick
Steven R Post
author_sort Ginell R Post
collection DOAJ
description Classic Hodgkin lymphoma (CHL) characteristically shows few malignant cells in a microenvironment comprised of mixed inflammatory cells. Although CHL is associated with a high cure rate, recent studies have associated poor prognosis with absolute monocyte count in peripheral blood and increased monocyte/macrophages in involved lymph nodes. Thus, the role of monocytic infiltration and macrophage differentiation in the tumor microenvironment of CHL may be more relevant than absolute macrophage numbers to defining prognosis in CHL patients and potentially have therapeutic implications. Most studies identify tumor-associated macrophages (TAMs) using markers (e.g., CD68) expressed by macrophages and other mononuclear phagocytes, such as monocytes. In contrast, Class A Scavenger Receptor (SR-A/CD204) is expressed by tissue macrophages but not monocytic precursors. In this study, we examined SR-A expression in CHL (n = 43), and compared its expression with that of other macrophage markers. We confirmed a high prevalence of mononuclear cells that stained with CD68, CD163, and CD14 in CHL lymph nodes. However, SR-A protein expression determined by immunohistochemistry was limited to macrophages localized in sclerotic bands characteristic of nodular sclerosis CHL. In contrast, SR-A protein was readily detectable in lymph nodes with metastatic tumor, extra-nodal CHL, T cell/histiocyte-rich large B cell lymphoma, and resident macrophages in non-malignant tissues, including spleen, lymph node, liver and lung. The results of SR-A protein expression paralleled the expression of SR-A mRNA determined by quantitative RT-PCR. These data provide evidence that tumor-infiltrating monocyte/macrophages in CHL have a unique phenotype that likely depends on the microenvironment of nodal CHL.
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spelling doaj.art-fa7bc9b658854104be253680ab20d3622022-12-21T19:13:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011411e022462110.1371/journal.pone.0224621Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.Ginell R PostYouzhong YuanEmily R HolthoffCharles M QuickSteven R PostClassic Hodgkin lymphoma (CHL) characteristically shows few malignant cells in a microenvironment comprised of mixed inflammatory cells. Although CHL is associated with a high cure rate, recent studies have associated poor prognosis with absolute monocyte count in peripheral blood and increased monocyte/macrophages in involved lymph nodes. Thus, the role of monocytic infiltration and macrophage differentiation in the tumor microenvironment of CHL may be more relevant than absolute macrophage numbers to defining prognosis in CHL patients and potentially have therapeutic implications. Most studies identify tumor-associated macrophages (TAMs) using markers (e.g., CD68) expressed by macrophages and other mononuclear phagocytes, such as monocytes. In contrast, Class A Scavenger Receptor (SR-A/CD204) is expressed by tissue macrophages but not monocytic precursors. In this study, we examined SR-A expression in CHL (n = 43), and compared its expression with that of other macrophage markers. We confirmed a high prevalence of mononuclear cells that stained with CD68, CD163, and CD14 in CHL lymph nodes. However, SR-A protein expression determined by immunohistochemistry was limited to macrophages localized in sclerotic bands characteristic of nodular sclerosis CHL. In contrast, SR-A protein was readily detectable in lymph nodes with metastatic tumor, extra-nodal CHL, T cell/histiocyte-rich large B cell lymphoma, and resident macrophages in non-malignant tissues, including spleen, lymph node, liver and lung. The results of SR-A protein expression paralleled the expression of SR-A mRNA determined by quantitative RT-PCR. These data provide evidence that tumor-infiltrating monocyte/macrophages in CHL have a unique phenotype that likely depends on the microenvironment of nodal CHL.https://doi.org/10.1371/journal.pone.0224621
spellingShingle Ginell R Post
Youzhong Yuan
Emily R Holthoff
Charles M Quick
Steven R Post
Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.
PLoS ONE
title Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.
title_full Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.
title_fullStr Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.
title_full_unstemmed Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.
title_short Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.
title_sort identification of a novel monocytic phenotype in classic hodgkin lymphoma tumor microenvironment
url https://doi.org/10.1371/journal.pone.0224621
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AT emilyrholthoff identificationofanovelmonocyticphenotypeinclassichodgkinlymphomatumormicroenvironment
AT charlesmquick identificationofanovelmonocyticphenotypeinclassichodgkinlymphomatumormicroenvironment
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