Abstract A10: L1236, a Hodgkin and Reed-Sternberg cell line, stimulates monocytes in vitro to differentiate into M2-like macrophages

Abstract

Abstract The microenvironment of classical Hodgkin lymphoma (cHL) is characterized by a small number of malignant Hodgkin and Reed-Sternberg (HRS) cells embedded in a background rich with infiltrating immune cells. HRS cells and the surrounding cellular infiltrates are believed to produce soluble and membrane-bound factors that are essential for the survival and proliferation of HRS cells. Steidl et al (2010) have reported that an increase in the number of tumor associated macrophages in cHL correlates with poor prognosis. However, little is known about the molecular crosstalk between macrophages and HRS cells in cHL. This study aims to examine in-vitro the influence of HRS cells on monocyte activation and differentiation. Freshly isolated human monocytes were co-cultured with L1236 cells, a HRS cell-line, under standard culture conditions. At the end of 8 days in culture, we examined the influence of HRS cells on monocyte survival and differentiation. In addition, we determined the activation and differentiation status of the co-cultured monocyte by assessing the cells for CD206 and IL-10 expression. The role of IL-4Rα and Macrophage colony-stimulating factor (M-CSF) receptor on HRS cell-induced monocyte differentiation was examined using antibody blocking assay. We also examined consented cHL patient samples for the presence of CD206/CD68 double positive macrophages by immunofluorescent staining. Our data showed that L1236 cells are able to enhance the survival of monocytes in vitro. In the presence of L1236 cells, monocytes differentiated into alternatively activated, M2-like macrophages which expressed CD206 and IL-10. The observed enhanced survival, and differentiation to M2-like macrophages, was mediated by soluble factors secreted by the L1236 cells. The survival of co-cultured monocytes is enhanced by signalling through the M-CSF receptor. In contrast, the differentiation to M2-like macrophages is in part, regulated by signals generated via IL-4Rα. Finally, the presence of CD68/CD206 double positive macrophages was detected in three out of four cHL patient samples. We conclude that HRS cells secrete soluble factors that can in vitro directly modulate monocyte survival and differentiation to a CD206+ M2 macrophage phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A10.