Universität zu Köln

Mellinghoff, Sibylle C. ORCID: 0000-0003-3928-2503, Thelen, Martin ORCID: 0000-0002-2785-9726, von Bergwelt‐Baildon, Michael, Schlößer, Hans A. ORCID: 0000-0002-1304-7719, Cornely, Oliver A. ORCID: 0000-0001-9599-3137, Sprute, Rosanne ORCID: 0000-0003-2457-6437, Stemler, Jannik ORCID: 0000-0001-9152-2469, Mayer, Leonie, Weskamm, Leonie Marie, Friedrich, Monika, Ly, My Linh, Dahlke, Christine and Addo, Marylyn M. (2025). Immune Phenotypes in Patients With Invasive Mould Infection Support the Use of PD ‐1 Inhibition as Potential Treatment Option. Mycoses, 68 (3). Wiley-Blackwell. ISSN 0933-7407

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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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Mellinghoff, Sibylle C. UNSPECIFIED https://orcid.org/0000-0003-3928-2503 UNSPECIFIED Thelen, Martin UNSPECIFIED https://orcid.org/0000-0002-2785-9726 UNSPECIFIED von Bergwelt‐Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlößer, Hans A. UNSPECIFIED https://orcid.org/0000-0002-1304-7719 UNSPECIFIED Cornely, Oliver A. UNSPECIFIED https://orcid.org/0000-0001-9599-3137 UNSPECIFIED Sprute, Rosanne UNSPECIFIED https://orcid.org/0000-0003-2457-6437 UNSPECIFIED Stemler, Jannik UNSPECIFIED https://orcid.org/0000-0001-9152-2469 UNSPECIFIED Mayer, Leonie UNSPECIFIED UNSPECIFIED UNSPECIFIED Weskamm, Leonie Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrich, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Ly, My Linh UNSPECIFIED UNSPECIFIED UNSPECIFIED Dahlke, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Addo, Marylyn M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-791973
Identification Number:	10.1111/myc.70044
Journal or Publication Title:	Mycoses
Volume:	68
Number:	3
Date:	17 March 2025
Publisher:	Wiley-Blackwell
ISSN:	0933-7407
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Medicine Unspecified
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Chirurgie > Klinik und Poliklinik für Allgemein-, Viszeral- und Tumorchirurgie Faculty of Medicine > Sonstiges > Centrum für integrierte Onkologie (CIO) Faculty of Medicine > Sonstiges > Zentrum für Klinische Studien Unspecified Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79197