Biology of Kaposi's sarcoma

Kaposi's sarcoma II(S) is an angioproliferative disease occurring in severa l different clinical-epidemiological forms that. however, share the same hi stological traits and are all associated with infection by the human herpes virus 8 (HHV8). KS initiates in a context of immune dysregulation character ised by CD8 + T cell activation and the production of Th 1-type cytokines t hat induce a generalised activation of endothelial cells leading to adhesio n and tissue extravasation of lympho-monocytes. spindle cell formation and angiogenesis. These phenomena are triggered or enhanced by infection with H HV8 that, in turn. is reactivated by the same cytokines. Productively-infec ted circulating cells are recruited into 'activated' tissue sites where HHV 8 finds an optimal environment for establishing a persistent, latent infect ion of KS spindle cells (KSC). HHV8 dissemination is favoured by virus esca pe mechanisms and immune dysregulation, and leads to immune responses that are not effective against the virus but, paradoxically, exacerbates the rea ctive process. Although early KS is a reactive process of polyclonal nature that can regress. in time it can progress in to a true sarcoma. Thr progre ssion of KS appears to be due to the deregulated expression of oncogenes an d oncosuppressor genes, to the long-lasting expression of the HHV8 latency genes and, for AIDS-KS, is promoted by the proliferative and angiogenic eff ects of the HIV-1 Tar protein. (C) 2001 Elsevier Science Ltd. All rights re served.