Immune Phenotypes in Patients With Invasive Mould Infection Support the Use of PD-1 Inhibition as Potential Treatment Option.

IF 4.1 2区医学 Q1 DERMATOLOGY

Mycoses Pub Date : 2025-03-01 DOI:10.1111/myc.70044

Sibylle C Mellinghoff, Martin Thelen, Michael von Bergwelt-Baildon, Hans A Schlößer, Oliver A Cornely, Rosanne Sprute, Jannik Stemler, Leonie Mayer, Leonie Marie Weskamm, Monika Friedrich, My Linh Ly, Christine Dahlke, Marylyn M Addo

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引用次数: 0

Abstract

Background: Invasive mould infections (IMI) cause substantial morbidity and mortality in populations at risk. Novel treatment approaches are urgently needed. Targeting immune checkpoints may reverse hyporesponsiveness of the innate and adaptive immune systems.

Methods: In this prospective, observational study, we investigated immune checkpoint expression levels on immune cells in patients with invasive aspergillosis (IA; n = 25) and mucormycosis (MU; n = 7). Healthy controls (HC; n = 5) and patients with matched haematological diseases but without IMI served as control populations (CP; n = 10). Multicolour flow cytometry analysis was used to compare immune cell subsets and the expression of immune-regulatory molecules in peripheral blood mononuclear cells (PBMCs).

Results: Lymphocyte subsets and immune phenotypes in PBMCs were similar between patients with IMI and haematological CP, except for regulatory T cells, which were increased in PBMCs of patients with IA and MU compared to HCs. In IA and MU, PBMCs showed increased expression of immune checkpoint molecules compared to healthy controls and matched haematological CP, with this effect being more pronounced in IA than in MU. We found heterogeneous, disease-, molecule-, and patient-specific expression patterns of immune checkpoint molecules. For example, PD-1 expression was highest in MU PBMCs, followed by IA PBMCs, while HC PBMCs showed lower expression levels. Overall mortality in our patient population was 44.0% (IPA) and 80.0% (MU).

Conclusions: We report an immune phenotype consistent with T-cell exhaustion in IMI, indicating potential contributions from haematological treatment, underlying disease, and infection. However, the primary underlying cause remains unclear and requires further investigation. A marker that was notably higher in IMI patients was PD-1, and treatment approaches specifically targeting this molecule may be promising.

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侵袭性霉菌感染患者的免疫表型支持使用 PD-1 抑制剂作为潜在的治疗方案

背景：侵袭性霉菌感染（IMI）在高危人群中引起大量发病率和死亡率。迫切需要新的治疗方法。靶向免疫检查点可以逆转先天和适应性免疫系统的低反应性。方法：在这项前瞻性观察性研究中，我们研究了侵袭性曲霉病(IA；n = 25)和毛霉病(MU；n = 7)。健康对照(HC；n = 5)和匹配的血液病但没有IMI的患者作为对照人群(CP；n = 10)。采用多色流式细胞术比较外周血单核细胞（PBMCs）免疫细胞亚群和免疫调节分子的表达。结果：IMI和血液学CP患者外周血淋巴细胞亚群和免疫表型相似，除了调节性T细胞，IA和MU患者外周血淋巴细胞的调节性T细胞比hc增加。在IA和MU中，与健康对照和匹配的血液学CP相比，pbmc显示免疫检查点分子的表达增加，并且这种影响在IA中比MU中更明显。我们发现免疫检查点分子的异质性、疾病特异性、分子特异性和患者特异性表达模式。例如，PD-1在MU PBMCs中表达最高，其次是IA PBMCs，而HC PBMCs表达水平较低。患者总体死亡率为44.0% （IPA）和80.0% （MU）。结论：我们报告了与IMI中t细胞耗竭一致的免疫表型，表明血液学治疗、基础疾病和感染可能起作用。然而，主要的潜在原因尚不清楚，需要进一步调查。在IMI患者中明显较高的标志物是PD-1，专门针对该分子的治疗方法可能很有希望。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mycoses 医学-皮肤病学

CiteScore

10.00

自引率

8.20%

发文量

143

审稿时长

6-12 weeks

期刊介绍： The journal Mycoses provides an international forum for original papers in English on the pathogenesis, diagnosis, therapy, prophylaxis, and epidemiology of fungal infectious diseases in humans as well as on the biology of pathogenic fungi. Medical mycology as part of medical microbiology is advancing rapidly. Effective therapeutic strategies are already available in chemotherapy and are being further developed. Their application requires reliable laboratory diagnostic techniques, which, in turn, result from mycological basic research. Opportunistic mycoses vary greatly in their clinical and pathological symptoms, because the underlying disease of a patient at risk decisively determines their symptomatology and progress. The journal Mycoses is therefore of interest to scientists in fundamental mycological research, mycological laboratory diagnosticians and clinicians interested in fungal infections.