Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors
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Salum J. Lidenge1,2,4,5, For Yue Tso1,2, Owen Ngalamika6, Jaydeep Kolape7, John R. Ngowi4, Julius Mwaiselage4,5, Charles Wood1,2,3 and John T. West1,3
1 Nebraska Center for Virology, Lincoln, NE, USA
2 School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA
3 Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA
4 Ocean Road Cancer Institute, Dar es Salaam, Tanzania
5 Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
6 Dermatology and Venereology Section, University Teaching Hospitals, University of Zambia School of Medicine, Lusaka, Zambia
7 Morrison Microscopy Core Facility, Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA
|John T. West,||email:||firstname.lastname@example.org|
Keywords: Kaposi’s sarcoma; HIV-1; KSHV; immune cells; tumor microenvironment
Received: February 18, 2020 Accepted: April 03, 2020 Published: April 28, 2020
Despite the close association between Kaposi’s sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. Therefore, their potential capacity to serve as prognostic biomarkers of KS disease progression or control is unclear. Because epidemic-KS (EpKS) occurs with HIV-1 co-infection, it is particularly important to compare TIIC between EpKS and HIV-negative African endemic-KS (EnKS) to dissect the roles of HIV-1 and Kaposi Sarcoma-associated herpesvirus (KSHV) in KS pathogenesis. This cross-sectional study of 13 advanced KS (4 EnKS, 9 EpKS) patients and 3 healthy controls utilized single-color immunohistochemistry and dual-color immunofluorescence assays to characterize and quantify KSHV infected cells in relation to various TIIC in KS biopsies. Analysis of variance (ANOVA) and Mann-Whitney tests were used to assess differences between groups where P-values < 0.05 were considered significant. The abundance of KSHV infected cells was heterogeneous in KS biopsies. Despite the presence of T-cell chemoattractant chemokine CxCL-9 in biopsies, CD8+ T-cells were sparsely distributed in regions with evident KSHV infected cells but were readily detectable in regions devoid of KSHV infected cells (P < 0.0001). CD68+ (M1) macrophages were evenly and diffusely distributed in KS biopsies, whereas, the majority of CD163+ (M2) macrophages were localized in regions devoid of KSHV infected cells (P < 0.0001). Overall, the poor immune cell infiltration or co-localization in KS biopsies independent of HIV-1 co-infection suggests a fundamental tumor immune evasion mechanism that warrants further investigation.
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