Hodgkin’s disease: A disorder of dysregulated cellular cross-talk

Abstract

Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including 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 result 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 cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.

Distinctive Epstein-Barr Virus Variants Associated with Benign and Malignant Pediatric Pathologies: LMP1 Sequence Characterization and Linkage with Other Viral Gene Polymorphisms

“…development of this malignancy is not fully understood, it is supposed that EBV rescues from apoptosis those B lymphocytes whose differentiation is faulty, probably by means of proliferative and antiapoptotic signals (22,29). The resemblance described for LMP1 variants among EBVrelated lymphomas and IM were made more evident when genomic arrangements, including EBNA3C, EBNA1, and BZLF1 along with LMP1 variants, were analyzed.…”

Glut1 and Glut3 expression in lymphoma and their association with tumor intensity on 18F-fluorodeoxyglucose positron emission tomography

“…their reactive neighboring cells are able to cross-talk through a complex network of cytokine-dependent and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and nonneoplastic cells, cHL cells may receive several proliferative and antiapoptotic signals, favoring the cellular expansion and tumor cell survival in cHL [22,23]. In a recent study by Tzankov et al [24], it was shown that 90% of the cHL cells were positive for proliferative cell nuclear antigen and 98% were positive for cyclin A.…”

Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma

“…8,9,13,25,26 Both mast cells and eosinophils are implicated in the stimulation of HRS cells, 4,18 and the number of these cell types in affected lymph nodes correlates with poor prognosis. [27][28][29] Thus, IL-9 may be of importance in HL development, regulating both HRS cells as well as infiltrating cells.…”

“…1,2 These different cytokines may also be responsible for sclerosis, tissue eosinophilia and the B-symptoms -night sweats, fever and weight loss -seen in many HL patients. 3,4 One cytokine associated with HL is interleukin-9 (IL-9). 5 This is a multifunctional cytokine mainly produced by stimulated T H 2-cells, first described to allow antigen-independent proliferation of murine T-helper cell clones, 6 and enhance proliferation in murine mast cell lines.…”