霍奇金-里德-斯登堡细胞上人类白细胞抗原(HLA)Ⅰ类的表达是典型霍奇金淋巴瘤微环境组成的主要决定因素,与 EBV 无关

IF 7.6 2区 医学 Q1 HEMATOLOGY
HemaSphere Pub Date : 2024-06-03 DOI:10.1002/hem3.84
Berit Müller-Meinhard, Nicole Seifert, Johanna Grund, Sarah Reinke, Fatih Yalcin, Helen Kaul, Sven Borchmann, Bastian von Tresckow, Peter Borchmann, Annette Plütschow, Julia Richter, Andreas Engert, Michael Altenbuchinger, Paul J. Bröckelmann, Wolfram Klapper
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引用次数: 0

摘要

典型霍奇金淋巴瘤(HL)中的霍奇金-里德-斯登堡细胞(HRSCs)经常缺乏人类白细胞抗原I类(HLA-I)的表达,这被认为会阻碍肿瘤微环境(TME)中细胞毒性T细胞的活化。在这里,我们证明了HRSCs上HLA-I的表达是TME组成的一个重要决定因素,而HLA-II的表达只与TME中微小的差异基因表达有关。在HLA-I阳性的HL中,HRSCs的含量和CCL17/TARC的表达量都很低,这与HRSCs中是否存在Epstein-Barr病毒无关。此外,HLA-I 阳性 HL 显示出 CD8+ 细胞毒性 T 细胞的高含量。不过,在靠近 HRSCs 的 CD8+ T 细胞上,抑制性免疫检查点 LAG3 的表达量有所增加。我们观察到TME中没有克隆扩增的T细胞,这表明细胞毒性活性受到干扰。虽然在我们的队列中,HLA-I 阳性 HL 与不利的临床病程无关,但它们与最近描述的 H2 亚型 HL 有着共同的特征。鉴于TME组成的重大差异,免疫检查点抑制剂在HLA-I阳性与HLA-I阴性HL中的作用机制可能有所不同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV-independent major determinant of microenvironment composition in classic Hodgkin lymphoma

Human leukocyte antigen (HLA) class I expression on Hodgkin–Reed–Sternberg cells is an EBV-independent major determinant of microenvironment composition in classic Hodgkin lymphoma

Hodgkin–Reed–Sternberg cells (HRSCs) in classic Hodgkin Lymphoma (HL) frequently lack expression of human leukocyte antigen class I (HLA-I), considered to hamper activation of cytotoxic T cells in the tumor microenvironment (TME). Here, we demonstrate HLA-I expression on HRSCs to be a strong determinant of TME composition whereas expression of HLA-II was associated with only minor differential gene expression in the TME. In HLA-I-positive HL the HRSC content and expression of CCL17/TARC in HRSCs are low, independent of the presence of Epstein–Barr virus in HRSCs. Additionally, HLA-I-positive HL shows a high content of CD8+ cytotoxic T cells. However, an increased expression of the inhibitory immune checkpoint LAG3 on CD8+ T cells in close proximity to HRSCs is observed. Suggesting interference with cytotoxic activity, we observed an absence of clonally expanded T cells in the TME. While HLA-I-positive HL is not associated with an unfavorable clinical course in our cohorts, they share features with the recently described H2 subtype of HL. Given the major differences in TME composition, immune checkpoint inhibitors may differ in their mechanism of action in HLA-I-positive compared to HLA-I-negative HL.

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来源期刊
HemaSphere
HemaSphere Medicine-Hematology
CiteScore
6.10
自引率
4.50%
发文量
2776
审稿时长
7 weeks
期刊介绍: HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology. In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care. Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.
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