Lack of CD8+ T-cell co-localization with Kaposi's sarcoma-associated herpesvirus infected cells in Kaposi's sarcoma tumors.
Lack of CD8+ T-cell co-localization with Kaposi's sarcoma-associated herpesvirus infected cells in Kaposi's sarcoma tumors.
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DOI：
10.18632/oncotarget.27569
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发表时间：
2020-04-28
期刊：
影响因子：
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通讯作者：
West, John T
中科院分区：
文献类型：
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作者：
Lidenge, Salum J;Tso, For Yue;West, John T
尽管卡波西肉瘤（KS）和免疫功能障碍之间的密切联系，它仍然不清楚是否肿瘤浸润免疫细胞（TIIC），通过他们的缺席，存在或功能障碍，与KS发病机制机制。因此，它们作为KS疾病进展或控制的预后生物标志物的潜在能力尚不清楚。由于非洲地方性KS（EpKS）与HIV-1合并感染发生，因此比较EpKS和HIV阴性非洲地方性KS（EnKS）之间的TIIC以剖析HIV-1和卡波西肉瘤相关疱疹病毒（KSHV）在KS发病机制中的作用尤为重要。这项对13名晚期KS（4名EnKS，9名EpKS）患者和3名健康对照的横断面研究利用单色免疫组织化学和双色免疫荧光测定来表征和量化KS活检中与各种TIIC相关的KSHV感染细胞。使用方差分析（ANOVA）和Mann-Whitney检验来评估组间差异，其中P值< 0.05被认为是显著的。KS活检组织中KSHV感染细胞的丰度是异质性的。尽管活检组织中存在T细胞趋化因子CxCL-9，但CD 8 + T细胞稀疏地分布在具有明显KSHV感染细胞的区域，但在没有KSHV感染细胞的区域中容易检测到（P < 0.0001）。在KS活检组织中，CD 68+（M1）巨噬细胞均匀弥散分布，而CD 163+（M2）巨噬细胞主要分布在无KSHV感染细胞的区域（P < 0.0001）。总的来说，KS活检中免疫细胞浸润或共定位不依赖于HIV-1共感染，这提示了一种基本的肿瘤免疫逃避机制，值得进一步研究。
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.