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

ABSTRACT: The inflammatory infiltrate plays a pivotal role in classical Hodgkin lymphoma (cHL). Here, we focussed on the role of macrophages (M?) and dendritic cells (DC).M? 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, M? stimulated with GM-CSF (M?GM-CSF, pro-inflammatory M?-1-model) or M-CSF (M?M-CSF, immunomodulatory M?-2-model) were incubated with cHL cell line (L1236, HDLM2) supernatants (SN). DC maturation or M? polarization were investigated by flow cytometry. Furthermore, the impact of DC or M? on cHL cell proliferation was analyzed by BrdU/CFSE assay.In cHL tissues mature myeloid (m)DC and M? predominated. High numbers of CD83+ mDC and low numbers of CD163+ M? 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 M? phenotype were promoted by SN derived from cHL cell lines. TNF? neutralization in SN resulted in a significant inhibition of mDC maturation. DC and pro-inflammatory M? inhibited the proliferation of cHL cells.Adopting an immunomodulatory phenotype is a potential mechanism for how M? promote immune evasion in cHL. Mature DC, in contrast, might participate in antitumoral immunity.

SUBMITTER: Tudor CS 

PROVIDER: S-EPMC4255018 | biostudies-other | 2014

REPOSITORIES: biostudies-other