Mast cells express functional CD30 ligand and are the predominant CD30L‐positive cells in Hodgkin's disease

Abstract

Summary. Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically doublestained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L±CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.

Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis

“…It has recently been shown that mast cells express functional CD30L/CD153 and are the predominant CD30L-positive cells in Hodgkin lymphoma. 44 In addition, functional CD30L has also been demonstrated in almost all mast cells of the HMC-1 mast cell leukemia cell line. 44 Thus, the demonstration of the consistent expression of CD30 in the majority of neoplastic mast cells in aggressive variants of systemic mastocytosis may argue for possible interactions between CD30 and its ligand, CD153, in neoplastic mast cells.…”

“…44 In addition, functional CD30L has also been demonstrated in almost all mast cells of the HMC-1 mast cell leukemia cell line. 44 Thus, the demonstration of the consistent expression of CD30 in the majority of neoplastic mast cells in aggressive variants of systemic mastocytosis may argue for possible interactions between CD30 and its ligand, CD153, in neoplastic mast cells. One possibility could be that CD30-CD153 interactions are involved in autocrine growth regulation.…”

TCR-Independent CD30 Signaling Selectively Induces IL-13 Production Via a TNF Receptor-Associated Factor/p38 Mitogen-Activated Protein Kinase-Dependent Mechanism

“…Second, IL-13 may act as a growth factor for certain tumors, promoting tumor expansion (39). In Hodgkin's disease, CD30 ϩ Reed-Sternberg (H/RS) cells are surrounded by nonneoplastic cells, many of which are mast cells expressing CD30L (40). IL-13 production following engagement of CD30 on T cells by CD30L on mast cells could potentially both directly promote growth of certain tumor types and reduce tumor elimination by T cells.…”

Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF

“…The expression of CD153 (CD30L) was observed on mast cells from patients with Hodgkin's diseases (40), suggesting the contribution of mast cell-derived CD153 to the pathology associated with the disorder. In this study we report for the first time the expression of CD153 on mouse BMCMCs (Fig.…”