Expression of PD-1 and PD-Ls in Kaposi's sarcoma and regulation by oncogenic herpesvirus lytic reactivation
Expression of PD-1 and PD-Ls in Kaposi's sarcoma and regulation by oncogenic herpesvirus lytic reactivation
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DOI：
10.1016/j.virol.2019.07.024
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发表时间：
2019-10-01
期刊：
影响因子：
3.7
通讯作者：
Qin, Zhiqiang
中科院分区：
文献类型：
--
作者：
Chen, Jungang;Del Valle, Luis;Qin, Zhiqiang
卡波西肉瘤相关疱疹病毒（KSHV）可引起多种癌症，如卡波西肉瘤（KS）和原发性渗出性淋巴瘤（PEL）。PD-1/PD-Ls免疫检查点分子在肿瘤细胞免疫逃逸中起重要作用。PD-1/PD-Ls的表达及其受致癌病毒（特别是KSHV）的调控在很大程度上仍不明确。在此，我们证明了来自HIV +患者队列的KS组织中的强PD-1/PD-L1/PD-L2表达。我们发现，诱导KSHV裂解性再激活显著上调感染肿瘤细胞上的PD-L1表达，可能是通过几种主要的细胞信号传导途径和IL-1 β，这可能代表了病毒相关肿瘤细胞免疫逃逸的新机制。
Kaposi's sarcoma-associated herpesvirus (KSHV) causes several cancers such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). PD-1/PD-Ls immune checkpoint molecules play important roles in cancer cell immune escape. The expression of PD-1/PD-Ls and their regulation by oncogenic viruses, in particular KSHV, remain largely undefined. Here we demonstrate strong PD-1/PD-Ll/PD-L2 expression in KS tissues from a cohort of HIV + patients. We found that induction of KSHV lytic reactivation significantly upregulates PD-L1 expression on infected tumor cells, potentially through several major cellular signaling pathways and IL-1 beta, which may represent a novel mechanism for virus-associated tumor cell immune escape.