HODGKINS-DISEASE - A DISORDER OF DYSREGULATED CELLULAR CROSS-TALK

Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Ho dgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic back ground of non-neoplastic (reactive) cells recruited and activated by H -RS cells-derived cytokines. H-RS cells can be functionally regarded a s antigen-presenting cells (APC) able to elicit an intense, but anergi c and ineffective, T-cell mediated immune response along with a hyperp lastic inflammatory reaction which involves several cell types includi ng T-and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a re sult of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS c ells may further contribute to the biologic and clinical progression o f HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander re active cell populations might be beneficial in the teatment of HD pati ents.