T-cell diversity and exclusion of blood-derived T-cells in the tumor microenvironment of classical Hodgkin Lymphoma

IF 12.8 1区 医学 Q1 HEMATOLOGY
Nicole Seifert, Sarah Reinke, Johanna Grund, Berit Müller-Meinhard, Julia Richter, Thorsten Heilmann, Hans Schlößer, Michaela Kotrova, Monika Brüggemann, Peter Borchmann, Paul J. Bröckelmann, Michael Altenbuchinger, Wolfram Klapper
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Abstract

The Tumor Microenvironment (TME) in classical Hodgkin Lymphoma (HL) contains abundant immune cells and only few neoplastic Hodgkin and Reed-Sternberg cells (HRSC). We analyzed the T-cell receptor (TCR) repertoire to detect T-cell expansion in the TME and blood. In contrast to solid cancer tissue, T-cells in the TME of HL are highly polyclonal at first diagnosis and show only minor clonal expansion during anti-PD1 immune checkpoint blockade (ICB). At relapse and during ICB, pre-amplified T-cell populations increase in the TME of solid cancers but to a much lesser extent in HL. In contrast, T-cell populations in the peripheral blood of HL patients display higher clonality than healthy controls reaching clonality levels comparable to solid cancer. However, pre-amplified blood T-cells in HL patients show only minor additional clonal expansion during ICB. Moreover, blood-derived T-cells do not repopulate the TME of HL to the same extent as observed in solid cancers. Thus, the T-cell repertoire in the TME of HL appears unique by a relatively low clonal T-cell content and the exclusion of clonally expanded T-cells from the peripheral blood. Exclusion of clonally expanded tumor-specific T-cells from the TME may present a novel mechanism of immune evasion in HL.

Abstract Image

经典霍奇金淋巴瘤肿瘤微环境中的 T 细胞多样性和血源性 T 细胞排斥作用
经典霍奇金淋巴瘤(HL)的肿瘤微环境(TME)中含有大量免疫细胞,只有少数肿瘤性霍奇金细胞和里德-斯特恩伯格细胞(HRSC)。我们分析了T细胞受体(TCR)谱系,以检测TME和血液中T细胞的扩增情况。与实体瘤组织不同,HL的TME中的T细胞在初诊时高度多克隆,在抗PD1免疫检查点阻断(ICB)期间仅表现出轻微的克隆扩增。在复发和 ICB 期间,实体瘤 TME 中的预扩增 T 细胞群会增加,但在 HL 中增加的程度要小得多。相比之下,HL 患者外周血中的 T 细胞群的克隆度高于健康对照组,达到了与实体癌相当的克隆度水平。然而,HL 患者的预扩增血液 T 细胞在 ICB 期间仅表现出轻微的额外克隆扩增。此外,血液中的 T 细胞在 HL 的 TME 中的重新填充程度与实体瘤中观察到的不同。因此,HL 的 TME 中的 T 细胞谱似乎是独特的,其克隆 T 细胞含量相对较低,外周血中排除了克隆扩增的 T 细胞。将克隆扩增的肿瘤特异性T细胞排除在TME之外可能是HL免疫逃避的一种新机制。
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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