Universität zu Köln

Mellinghoff, Sibylle C., Thelen, Martin ORCID: 0000-0002-2785-9726, Bruns, Christiane, Garcia-Marquez, Maria, Hartmann, Pia, Lammertz, Tatjana, Lehmann, Jonas, Nowag, Angela, Stemler, Jannik ORCID: 0000-0001-9152-2469, Wennhold, Kerstin, Cornely, Oliver A. ORCID: 0000-0001-9599-3137, Von Bergwelt-Baildon, Michael S. and Schloesser, Hans A. (2022). T-cells of invasive candidiasis patients show patterns of T-cell-exhaustion suggesting checkpoint blockade as treatment option. J. Infect., 84 (2). S. 237 - 248. LONDON: W B SAUNDERS CO LTD. ISSN 1532-2742

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Abstract

Objective: Recent data imply that strengthening host immunity by checkpoint inhibition improves outcome in invasive fungal infections (IFI), particularly in candidiasis. Methods: To assess T-cell exhaustion in this context, we compared peripheral blood mononuclear cells (PBMCs) and serum samples of patients with invasive Candida albicans infection (IC, n = 21) to PBMCs or tumor-infiltrating lymphocytes (TILs) from cancer patients (n = 14) and PBMCs of healthy controls (n = 20). Type and differentiation of lymphocytes and expression of 29 immune-regulatory molecules were analyzed by flow cytometry. C. albicans specific responses were assessed by FluoroSpot (n = 8) and antibody measurement (n = 14). Results: Fractions and phenotypes of lymphocyte subsets in PBMCs of IC patients were similar compared to PBMCs of controls, while they were different in TILs. PBMCs of patients with IC showed increased expression of immune-checkpoint molecules. The pattern of upregulated molecules was similar to TILs, but not present in PBMCs of control cancer patients. Fractions of T-cells expressing PD-1 and TIGIT were higher in IC patients that died. FluoroSpot analysis showed a Candida-specific IFN-y or IL-2 response in 5/8 patients, enhanced by addition of nivolumab in vitro. Conclusions: Together with preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment. (C) 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mellinghoff, Sibylle C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, Martin UNSPECIFIED orcid.org/0000-0002-2785-9726 UNSPECIFIED Bruns, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-Marquez, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lammertz, Tatjana UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Jonas UNSPECIFIED UNSPECIFIED UNSPECIFIED Nowag, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Stemler, Jannik UNSPECIFIED orcid.org/0000-0001-9152-2469 UNSPECIFIED Wennhold, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED orcid.org/0000-0001-9599-3137 UNSPECIFIED Von Bergwelt-Baildon, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloesser, Hans A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-685326
DOI:	10.1016/j.jinf.2021.12.009
Journal or Publication Title:	J. Infect.
Volume:	84
Number:	2
Page Range:	S. 237 - 248
Date:	2022
Publisher:	W B SAUNDERS CO LTD
Place of Publication:	LONDON
ISSN:	1532-2742
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PD-1; IL-17 Multiple languages Infectious Diseases Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68532