Dendritic cells and apoptosis in mycosis fungoides

Abstract

The existence of an effective antitumour immune response in mycosis fungoides (MF) has been shown by the isolation of tumour-specific T-cell clones from such patients. Dendritic cells (DCs) are considered crucial for the induction of immunity, including resistance to tumours. Apoptotic tumour cells are a major source for tumour antigens processed and presented by DCs via cross-presentation. The production of interleukin (IL)-10 by MF tumour cells is acknowledged and may block DCs maturation leading to tumour tolerance. Cross-presentation of apoptotic tumour cells by DCs will induce immunity if the DCs mature, but tolerance if maturation does not occur. We now further characterize the DCs in skin infiltrates of patch/plaque-stage MF (PS) and tumour-stage MF (TS) in situ. Secondly, we demonstrate apoptosis in MF infiltrates in situ and analyse the association of apoptotic cells to immature DCs, mature DCs and IL-10-positive cells. Immunohistochemical staining (single, double, triple) employing novel markers specific for immature and mature DCs, IL-10 and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) test were done on representative skin biopsies from PS and TS. In PS, the immature DCs are mostly lag/langerin + Langerhans cells (LCs). In the epidermis of PS, LCs predominate over fully mature DCs (non-LC type, CD83+, DC-lamp+). In the dermis of PS and TS, equal numbers of mature and immature (CD1a+, CD1c+) DCs are densely interspersed between the lymphocytic infiltrate. In TS, immature DCs mostly lack lag or langerin expression. Immature DCs with incorporated apoptotic cells were found rarely in PS but increasingly in TS. By triple staining in situ we could now show that strongly IL-10+ cells frequently surround immature DCs, some of them with incorporated apoptotic cells. CONCLUSIONS; DCs in MF perform a dual role, namely induction and maintenance of antitumour immunity, or, under less favourable circumstances such as production of IL-10 downregulation of antitumour immunity. The latter condition was mainly seen in TS, possibly explaining disease progression. Further in vitro studies are now required illuminating the role of DCs for the antitumour immune response in MF.