Open AccessHigh CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination
Author(s) -
Arlt Annekatrin,
Bonin Frederike,
Rehberg Thorsten,
PerezRubio Paula,
Engelmann Julia C.,
Limm Katharina,
Reinke Sarah,
Dullin Christian,
Sun Xueni,
Specht Rieke,
Maulhardt Markus,
Linke Franziska,
Bunt Gertrude,
Klapper Wolfram,
Vockerodt Martina,
Wilting Jörg,
Pukrop Tobias,
Dettmer Katja,
Gronwald Wolfram,
Oefner Peter J.,
Spang Rainer,
Kube Dieter
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12616
Subject(s) - mannose receptor , cd163 , tumor microenvironment , lymphoma , biology , macrophage , tumor associated macrophage , cancer research , immunology , pathology , microbiology and biotechnology , immune system , in vitro , medicine , biochemistry
Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 ( MRC1 )/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination.