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Abstract：
BACKGROUND: Classic Hodgkin lymphoma (cHL) is a lymphoid malignancy in which the microenvironment, where the neoplastic cells are immersed, contributes to the lymphomagenesis process. Epstein-Barr virus (EBV) presence also influences cHL microenvironment composition and contributes to pathogenesis. An increase in PDL1 expression in tumor cells and at the microenvironment was demonstrated in adult cHL. Therefore, our aim was to assess PD1/PDL1 pathway and EBV influence on this pathway in pediatric cHL, given that in Argentina, our group proved a higher incidence of EBV-associated pediatric lymphoma in children.
METHODS: For that purpose, EBV presence was assessed by in situ hybridization, whereas PD1 and PDL1 expressions were studied by immunohistochemistry. PDL1 genetic alterations were analyzed by FISH, and survival was evaluated for PD1 and PDL1 expressions.
RESULTS: EBV presence demonstrated no influence neither on PD1 expression at the microenvironment nor on PDL1 expression at HRS tumor cells. Unexpectedly, only 38% pediatric cHL displayed PDL1 genetic alterations by FISH, and no difference was observed regarding EBV presence. However, in EBV-related cHL cases, a higher number of PDL1 + cells were detected at the microenvironment.
CONCLUSIONS: Even though a high cytotoxic environment was previously described in EBV-related pediatric cHL, it might be counterbalanced by an immunoregulatory micro-environmental PDL1 + niche. This regulation may render a cytotoxic milieu that unsuccessfully try to eliminate EBV + Hodgkin Reed Sternberg tumor cells in pediatric patients.
METHODS: For that purpose, EBV presence was assessed by in situ hybridization, whereas PD1 and PDL1 expressions were studied by immunohistochemistry. PDL1 genetic alterations were analyzed by FISH, and survival was evaluated for PD1 and PDL1 expressions.
RESULTS: EBV presence demonstrated no influence neither on PD1 expression at the microenvironment nor on PDL1 expression at HRS tumor cells. Unexpectedly, only 38% pediatric cHL displayed PDL1 genetic alterations by FISH, and no difference was observed regarding EBV presence. However, in EBV-related cHL cases, a higher number of PDL1 + cells were detected at the microenvironment.
CONCLUSIONS: Even though a high cytotoxic environment was previously described in EBV-related pediatric cHL, it might be counterbalanced by an immunoregulatory micro-environmental PDL1 + niche. This regulation may render a cytotoxic milieu that unsuccessfully try to eliminate EBV + Hodgkin Reed Sternberg tumor cells in pediatric patients.
摘要：
背景：经典霍奇金淋巴瘤（cHL）是一种淋巴恶性肿瘤，其中微环境，肿瘤细胞浸入的地方，有助于淋巴生成过程。EB病毒（EBV）的存在也会影响cHL微环境组成并有助于发病机理。在成人cHL中证明了肿瘤细胞和微环境中PDL1表达的增加。因此,我们的目的是评估PD1/PDL1通路和EBV对小儿cHL通路的影响，鉴于在阿根廷，我们组证明了儿童中EBV相关小儿淋巴瘤的发病率较高.
方法：为此，通过原位杂交评估EBV的存在，而PD1和PDL1的表达通过免疫组织化学研究。PDL1基因改变通过FISH分析，并评估PD1和PDL1表达的生存率。
结果：EBV的存在表明对微环境中的PD1表达和HRS肿瘤细胞中的PDL1表达均无影响。出乎意料的是,只有38%的小儿cHL通过FISH显示PDL1基因改变，关于EBV的存在没有观察到差异。然而,在EBV相关的cHL病例中，在微环境中检测到较高数量的PDL1+细胞.
结论：尽管先前在EBV相关的小儿cHL中描述了高细胞毒性环境，它可能会被免疫调节微环境PDL1+生态位抵消。这种调节可能会导致细胞毒性环境，无法成功消除儿科患者的EBV霍奇金里德·斯特恩伯格肿瘤细胞。
方法：为此，
结果：EBV的存在表明对微环境中的PD1表达和HRS肿瘤细胞中的PDL1表达均无影响。
结论：尽管先前在EBV相关的小儿cHL中描述了高细胞毒性环境，
