Immunological and Inflammatory Features of Kaposi’s Sarcoma and Other Kaposi’s Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Associated Neoplasias

During the last 15 years, virologic and immunologic studies have provided a series of valuable clueson the modalities of γ-herpesvirus-induced oncogenesis, which do not only consist of the directsubversion of intracellular signaling pathways, leading to a frank neoplastic molecular network in theinfected cell, but also rely on viral manipulations of the cellular and cytokine microenvironment, especiallyin conditions of immunodeficiency in the host. At the virus-host interface, something iniquitous, strikinglyfavoring the aggressive expansion of human herpesvirus 8-infected lympho-endothelial clones, knownas Kaposi’s sarcoma, often occurs in different types of immunocompromised patients, able to establisha deleterious “pro-Kaposi’s sarcomaâ€? neo-angiogenic inflammatory network. However, these patientsmay control – or even resolve – the neoplastic burden as soon as an immunologic reassessment restoresfunctional anti-Kaposi’s sarcoma immune responses and reconstitutes a proper inflammatory environment.Indeed, the occurrence of iatrogenic Kaposi’s sarcoma remissions, after the reduction or switch ofimmunosuppressive regimens, strongly suggests that the reset of immunologic constraints characterizingthe Kaposi’s sarcoma onco-pathogenic system may be sufficient to inhibit human herpesvirus 8-positivelympho-endothelial proliferations. Accordingly, immunologic reports all underline the pivotal protectiverole of anti-human herpesvirus 8 memory T-cells (harmonically, both CD8+ and CD4+ subsets), thusdefinitely implying a general requirement for an effective, antiviral immuno-inflammatory environment,based on correct and productive interactions between different compartments of dendritic, myeloid,and specific T-cells, in order to achieve and maintain optimal control on human herpesvirus 8-associatedantigenic stimulations and Kaposi’s sarcoma disease.In this review, we recapitulate some remarkable features about the outstanding immunologic issueraised by human herpesvirus 8-driven neoplastic outgrowths in immunodeficient patients, and inparticular, we discuss the emerging view of Kaposi’s sarcoma as an atypical neoplastic process,tightly dependent on immune system dynamics. It is conceivable that functional dissection of thespecific immune responses, capable to cope with human herpesvirus 8, and further definitions of aglobal inflammatory profile with protective activity against Kaposi’s sarcoma outbreaks, will eventuallyfoster immunologic monitoring protocols during the follow-up of AIDS and posttransplant patients,either preventing or treating human herpesvirus 8-related tumors by multifunctional immunomodulationor prompt development of adoptive immunotherapeutic approaches.