Hodgkin's 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 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.
Pinto
A
A
The Leukemia Unit, I.R.C.C.S., Aviano, Italy. apinto@ets.it
Gattei
V
V
Zagonel
V
V
Aldinucci
D
D
Degan
M
M
De Iuliis
A
A
Rossi
F M
FM
Tassan Mazzocco
F
F
Godeas
C
C
Rupolo
M
M
Poletto
D
D
Gloghini
A
A
Carbone
A
A
Gruss
H J
HJ
D002450:Cell Communication / Q000502:physiology*; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans