Kaposi's sarcoma pathogenesis: a link between immunology and tumor biology.
Kaposi's sarcoma (KS) was a rare disease in Europe and North America until a decade ago, when it became the most common neoplasm complicating the acquired immunodeficiency syndrome (AIDS), where it acquires an aggressive course. Clinical and experimental data suggest that, at least in early stage, KS may not be a true sarcoma, but an hyperplastic-proliferative lesion that may regress. At least three components characterize KS lesions: (1) neoangiogenesis and proliferation of spindle-shaped cells of endothelial and macrophage cell origin, some of which may originate from a circulating precursor; (2) a cellular infiltrate represented by macrophages, lymphoid cells, mast cells, and neutrophils; and (3) the infection of spindle cells and mononuclear cells with a new virus of the Herpesvirinae family defined KS-associated herpesvirus or human herpesvirus-8 (HHV-8). KS lesions are highly responsive, in terms of growth, to inflammatory cytokines (IC) and many lesional cell components are able to secrete cytokines and chemokines, which induce paracrine-autocrine mechanisms of growth, angiogenesis, and promote further cellular recruitment. The association between HHV-8 and KS is close; however, the role of the virus in KS development is yet unknown. Nevertheless, the virus has the potential to encode for homologs of cellular cytokines and some chemokines and its reactivation is sensitive to stimuli provided by IC. This review focuses on these aspects of KS pathogenesis, trying to reconcile many of the clinical and experimental observations. Finally, the role of the HIV-1 Tat protein as a factor of progression in AIDS-KS as well as the role of cellular and HHV-8 encoded proto-oncogenes as factors and markers of progression of KS to a true malignancy is reviewed.
Ensoli
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B
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Sirianni
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MC
D000818:Animals; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D018450:Disease Progression; D015696:Gene Products, tat / Q000235:genetics; D015497:HIV-1 / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000209:etiology; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000276:immunology* / Q000821:virology; D054322:tat Gene Products, Human Immunodeficiency Virus