ArticlePLoS pathogens2012
Human Herpesvirus 8 (HHV8) sequentially shapes the NK cell repertoire during the course of asymptomatic infection and Kaposi sarcoma.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 61 citations in OpenAlex.
- Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly.Cancer research communications · 2024Trial
- Review
- From mechanism to therapy: the journey of CD24 in cancer.Frontiers in immunology · 2024Review
- The impact of HLA polymorphism on herpesvirus infection and disease.Immunogenetics · 2023Review
- Review
- Mesenchymal stem cells and natural killer cells interaction mechanisms and potential clinical applications.Stem cell research & therapy · 2022Review
- Article
- Kaposi's Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi's Sarcoma.Cancers · 2021Review
- Histopathological patterns and topographical distribution of Kaposi Sarcoma at Muhimbili National Hospital, Tanzania.African health sciences · 2021Article
- Review
- KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection.Cell reports · 2021Article
- Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine ProductionFrontiers in immunology · 2021Article
- Prospects for NK Cell Therapy of Sarcoma.Cancers · 2020Review
- Review
- The Presence of Antibody-Dependent Cell Cytotoxicity-Mediating Antibodies in Kaposi Sarcoma-Associated Herpesvirus-Seropositive Individuals Does Not Correlate with Disease Pathogenesis or Progression.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Cells of the Innate and Adaptive Immune Systems in Kaposi's Sarcoma.Journal of immunology research · 2020Review
- NK Cell Hyporesponsiveness: More Is Not Always Better.International journal of molecular sciences · 2019Review
- Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells.Trends in biochemical sciences · 2019Review
- Natural killer group 2D receptor and its ligands in cancer immune escape.Molecular cancer · 2019Review
- Progressive Impairment of NK Cell Cytotoxic Degranulation Is Associated With TGF-β1 Deregulation and Disease Progression in Pancreatic Cancer.Frontiers in immunology · 2019Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The contribution of innate immunity to immunosurveillance of the oncogenic Human Herpes Virus 8 (HHV8) has not been studied in depth. We investigated NK cell phenotype and function in 70 HHV8-infected subjects, either asymptomatic carriers or having developed Kaposi's sarcoma (KS). Our results revealed substantial alterations of the NK cell receptor repertoire in healthy HHV8 carriers, with reduced expression of NKp30, NKp46 and CD161 receptors. In addition, down-modulation of the activating NKG2D receptor, associated with impaired NK-cell lytic capacity, was observed in patients with active KS. Resolution of KS after treatment was accompanied with restoration of NKG2D levels and NK cell activity. HHV8-latently infected endothelial cells overexpressed ligands of several NK cell receptors, including NKG2D ligands. The strong expression of NKG2D ligands by tumor cells was confirmed in situ by immunohistochemical staining of KS biopsies. However, no tumor-infiltrating NK cells were detected, suggesting a defect in NK cell homing or survival in the KS microenvironment. Among the known KS-derived immunoregulatory factors, we identified prostaglandin E2 (PGE2) as a critical element responsible for the down-modulation of NKG2D expression on resting NK cells. Moreover, PGE2 prevented up-regulation of the NKG2D and NKp30 receptors on IL-15-activated NK cells, and inhibited the IL-15-induced proliferation and survival of NK cells. Altogether, our observations are consistent with distinct immunoevasion mechanisms that allow HHV8 to escape NK cell responses stepwise, first at early stages of infection to facilitate the maintenance of viral latency, and later to promote tumor cell growth through suppression of NKG2D-mediated functions. Importantly, our results provide additional support to the use of PGE2 inhibitors as an attractive approach to treat aggressive KS, as they could restore activation and survival of tumoricidal NK cells.
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