title: Macrophages and dendritic cells as actors in the immune reaction of classical Hodgkin lymphoma.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Christiane Silke
authors.initials: CS
authors.lastname: Tudor
authors.affiliation: Department of Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, University Hospital, 91054 Erlangen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Bruns
authors.affiliation: Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, University Hospital, 91054 Erlangen, Germany.
authors.forename: Luitpold Valentin
authors.initials: LV
authors.lastname: Distel
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, University Hospital, 91054 Erlangen, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Gerbitz
authors.affiliation: Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Maike Julia
authors.initials: MJ
authors.lastname: Buettner
mesh_terms: D000293:Adolescent; D000328:Adult; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006689:Hodgkin Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016207:Cytokines