HIV感染与霍奇金淋巴瘤中肿瘤微环境适应性免疫反应受损有关。
HIV infection is associated with compromised tumor microenvironment adaptive immune reactivity in Hodgkin Lymphoma.
发表日期：2024 Aug 08
作者：
Amanda Chantziou, Cloé Brenna, Kalliopi Ioannidou, Oliver Y Chen, Penelope A Korkolopoulou, Anastasia Antoniadou, Mina Psichogiou, Maria Papaioannou, Panagiotis Tsirigotis, Periklis G Foukas, Laurence L de Leval, Constantinos Petrovas
来源：
Blood Advances
摘要：
人类免疫缺陷病毒 (HIV) 感染对经典霍奇金淋巴瘤 (cHL) 肿瘤微环境 (TME) 的影响尚不清楚，经典霍奇金淋巴瘤 (cHL) 是 HIV 感染后最常见的并发症之一。在这里，我们采用多重免疫荧光 (mIF) 和空间转录组分析来剖析病毒感染（EBV、HIV/EBV）对 cHL TME 的影响。与 HIV-EBV- 相比，HIV-EBV cHL TME 的特点是共表达抑制性受体（PD-1、TIGIT）的 CD8high T 细胞、巨噬细胞亚群的细胞密度更高，以及与 TCR 表达增加相关的原位炎症分子谱和 BCR 细胞信号通路。与 HIV-EBV 相比，HIV EBV cHL TME 的特点是共表达 PD-1 和 TIGIT 的 CD8high T 细胞明显减少，这一特征伴随着 CD155high 肿瘤细胞的细胞密度显着增加。在 HIV EBV cHL TME 中发现原位 TCR 信号传导显着下调和细胞外基质重组途径上调，这与 CXCL13 和硫酸乙酰肝素（一种细胞外基质糖胺聚糖）拓扑结构的改变一致。我们的数据揭示了病毒感染时 cHL TME 细胞和分子组成的复杂性，可能对组合免疫疗法产生影响。此外，数据表明了进一步研究的具体分子靶点和途径，可以提高我们对 HIV 和淋巴瘤发生之间可能的机制联系的理解。版权所有 © 2024 美国血液学会。
The impact of Human Immunodeficiency Virus (HIV) infection on the tumor microenvironment (TME) of classic Hodgkin lymphoma (cHL), one of the most common co-morbidities following HIV infection, is not well understood. Here, we have employed multiplexed immunofluorescence (mIF) and spatial transcriptomic analysis to dissect the impact of viral infections (EBV, HIV/EBV) on cHL TME. Compared to HIV-EBV-, HIV-EBV+ cHL TME was characterized by higher cell densities of CD8high T cells co-expressing inhibitory receptors (PD-1, TIGIT), macrophage subsets and an in situ inflammatory molecular profile associated with increased expression of TCR and BCR cell signaling pathways. Compared to HIV-EBV+, HIV+EBV+ cHL TME was characterized by significantly less CD8high T cells co-expressing PD-1 and TIGIT, a profile concomitant with significantly increased cell densities of CD155high neoplastic cells. Significant downregulation of in situ TCR-signaling and upregulation of extracellular matrix reorganization pathways were found in HIV+EBV+ cHL TME, in line with an altered topological organization of CXCL13 and heparan sulfate, an extracellular matrix glycosaminoglycan. Our data reveal the complexity of the cellular and molecular composition of cHL TME in the presence of viral infections, with possible implications for combinatorial immunotherapies. Furthermore, the data suggest specific molecular targets and pathways for further investigation that could improve our understanding of possible mechanistic links between HIV and lymphomagenesis.Copyright © 2024 American Society of Hematology.