Hodgkin Lymphoma – an Interplay Between Tumour Cell and Microenvironment

• Main Author: Glimelius, Ingrid
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi 2009
• Subjects: MEDICINE; MEDICIN
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-100593; http://nbn-resolving.de/urn:isbn:978-91-554-7494-2

Hodgkin lymphoma (HL) is a malignant disorder characterised by few tumour cells surrounded by a massive infiltrate of inflammatory cells, fibrosis, and microvessels. Therefore, it is a good model in which to study the interplay between tumour cells and the microenvironment. In a population-based series, stage IIB had poor prognosis, equivalent to the most advanced stage (stage IV). The most prominent negative prognostic factor was tumour bulk in the mediastinum (often large fibrotic tumours). The tumour cells expressed interleukin-9 (IL-9) in their cytoplasm in half of the cases. These cases had an over representation of nodular sclerosis histology (characterised by fibrotic bands) and infiltration of eosinophils and mast cells in the tumours. Despite this, IL-9 expression was not a negative prognostic factor. A role of inflammatory cells is to contribute to angiogenesis. Yet, a correlation between high microvessel count and high mast cell number in HL tumours was not identified, in contrast to other lymphomas. However, a correlation to poor prognosis was seen for cases with high microvessel count. Eosinophils contain eosinophil cationic protein (ECP). ECP was cytotoxic to cells from two HL cell lines of B-cell origin and one HL line of T-cell origin. At high concentrations, the cytotoxic effect was not as pronounced for the line of T-cell origin. If the in vitro cell lines are representative of HL in vivo, eosinophils may have different roles in different HL tumours. In addition to the effect from tumour cells, host-related factors contribute to the inflammatory infiltrate in HL. A history of asthma and hives, and carrying the ECP434GG genotype were associated with elevated numbers of eosinophils, whereas, history of tobacco smoking was associated with lower numbers. HL is a complex tumour consisting of recruited and subverted normal cells, fibrosis and angiogenesis: these constitute the microenvironment, which likely supports tumour cell growth, and differs between patients.