Interactions between tissue fibroblasts in lymph nodes and Hodgkin/Reed-Sternberg cells

Leukemia & Lymphoma
Donatella AldinucciValter Gattei

Abstract

Classic Hodgkin's Disease (cHD) is a lymphoid neoplasia characterized by a few malignant Hodgkin and Reed-Sternberg (H-RS) cells embedded in an abundant background of non-tumor cells. In this context, fibrosis is a common morphologic feature of HD lesions, being found more frequently in cHD subtypes. The clinical and histopathologic features of cHD are thought to be largely due to the effects of a wide variety of cytokines and chemokines primarily produced by H-RS cells, as well as by the surrounding reactive component. In the present review, first we propose three mechanisms putatively explaining fibroblast activation and fibrosis in HD: (1) unbalanced production of the pro-fibrogenic Th2 over Th1 cytokines; (2) production of TGF-beta, b-FGF and IL-13 by H-RS cells; (3) activation of fibroblasts by CD40L-expressing cells of the HD microenvironment. Second, we suggest some molecular pathways involving cytokines produced by HD-derived fibroblasts (SCF, IL-7, IL-6) supposedly responsible for H-RS proliferation and rescue from apoptosis. Finally, we describe the role of specific molecules produced by H-RS cells in the regulation of HD-derived fibroblast production of chemokines, in turn involved in T-lymphocytes and recruitment of...Continue Reading

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