Macrophages and dendritic cells as actors in the immune reaction of classical Hodgkin lymphoma

• Published in: PloS one 2014-12, Vol.9 (12), p.e114345-e114345
• Main Authors: Tudor, Christiane Silke, Bruns, Heiko, Daniel, Christoph, Distel, Luitpold Valentin, Hartmann, Arndt, Gerbitz, Armin, Buettner, Maike Julia
• Format: Article
• Language: English
• Subjects: Actors; Actresses; Adolescent; Adult; Analysis; Antigens; Apoptosis; Biology and Life Sciences; Breast cancer; CD163 antigen; CD83 antigen; Cell Count; Cell Line, Tumor; Cell Proliferation; Cloning; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - physiology; Female; Flow cytometry; Gene expression; Granulocyte-macrophage colony-stimulating factor; Granulocytes; Hematology; Hodgkin Disease - immunology; Hodgkin Disease - mortality; Hodgkin Disease - pathology; Hodgkin's disease; Hodgkin's lymphoma; Humans; Immune response; Immunity; Immunity, Cellular; Immunohistochemistry; Immunomodulation; Infiltration; Inflammation; Interleukin 1; Interleukin 13; Kaplan-Meier Estimate; Ligands; Lymphoma; Macrophage colony stimulating factor; Macrophages; Macrophages - physiology; Male; Maturation; Medical prognosis; Medicine and Health Sciences; Middle Aged; Monocytes; Morphology; Neutralization; Non-Hodgkin's lymphomas; Oncology; Pathology; Peripheral blood; Phenotypes; Software; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114345

The inflammatory infiltrate plays a pivotal role in classical Hodgkin lymphoma (cHL). Here, we focussed on the role of macrophages (MΦ) and dendritic cells (DC). MΦ and DC infiltration was investigated in 106 cHL specimens using immunohistochemistry and cytokine expression was analyzed in a subset by real-time PCR. Human peripheral blood-derived monocytes, DC, MΦ stimulated with GM-CSF (MΦGM-CSF, pro-inflammatory MΦ-1-model) or M-CSF (MΦM-CSF, immunomodulatory MΦ-2-model) were incubated with cHL cell line (L1236, HDLM2) supernatants (SN). DC maturation or MΦ polarization were investigated by flow cytometry. Furthermore, the impact of DC or MΦ on cHL cell proliferation was analyzed by BrdU/CFSE assay. In cHL tissues mature myeloid (m)DC and MΦ predominated. High numbers of CD83+ mDC and low numbers of CD163+ MΦ were associated with improved disease specific survival. In numerous cHL specimens increased levels of both pro- and anti-inflammatory cytokines and of IL13 and GM-CSF were observed compared to reactive lymphadenopathies. Maturation of DC and induction and maintenance of an immunomodulatory MΦ phenotype were promoted by SN derived from cHL cell lines. TNFα neutralization in SN resulted in a significant inhibition of mDC maturation. DC and pro-inflammatory MΦ inhibited the proliferation of cHL cells. Adopting an immunomodulatory phenotype is a potential mechanism for how MΦ promote immune evasion in cHL. Mature DC, in contrast, might participate in antitumoral immunity.