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Abstract
Discussion Forum (0)
Abstract number: 3779

Session Type: ePosters

Session Title: ePosters

Authors(s): S. Mellinghoff (1), M. Thelen (2), M. Garcia-Marquez (2), P. Hartmann (3), J. Lehmann (2), N. Angela (3), J. Stemler (1), K. Wennhold (2), O.A. Cornely (1), M. Bergwelt-Baildon (4), H.A. Schloesser (2)

Authors Affiliations(s): (1) University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Germany, (2) Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Germany, (3) Wisplinghoff Laboratories, Germany, (4) Department of Medicine III, University Hospital, LMU Munich, Germany

Background:

Recently published in vitro and in vivo studies imply that strengthening host immunity may improve outcome in invasive fungal infections (IFI). Preclinical and clinical investigations suggest a potential benefit of checkpoint inhibition in IFI and particularly in candidiasis. We here report our findings of comprehensive prospective phenotyping of circulating lymphocytes in patients with invasive candidiasis (IC) by Candida albicans.

Methods:

Patients (n=21) with IC, including candidemia, were included. Peripheral blood mononuclear cells (PBMCs) and serum samples of healthy controls (n=20) as well as PBMC and tumour-infiltrating lymphocytes (TILs) obtained from colorectal (n=6) and non-small cell lung (n=8) cancer patients served as control populations. Type and differentiation states of lymphocytes and the expression of 30 immune-regulatory molecules in PBMCs and TILs of study subjects were analysed by flow cytometry. Candida albicans specific cellular and humoral responses were assessed by fluorospot and antibody measurement, respectively.

Results:

Fractions and phenotypes of lymphocyte subsets in PBMC of IC patients were similar compared to PBMC controls, while they were different in TILs. PBMCs of patients with IC but not CA showed increased expression of immune-checkpoint molecules, which paralleled TILs (Figure 1). Expression patterns of co-inhibitory molecules were similar in IC PBMCs and TILs. Expression of PD-1 and TIGIT was higher in patients that died and fluorospot analysis of three representative IC patients showed a Candida-specific IL-2 response in one patient, which was enhanced using nivolumab in vitro (Figure 2).

Conclusions:

The expression patterns and the similarities between IC PBMCs and TILs implies a potentially beneficial effect of immune-checkpoint inhibition in IC patients. Together with robust preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment.



COI Institutional Grants: Yes
Abstract number: 3779

Session Type: ePosters

Session Title: ePosters

Authors(s): S. Mellinghoff (1), M. Thelen (2), M. Garcia-Marquez (2), P. Hartmann (3), J. Lehmann (2), N. Angela (3), J. Stemler (1), K. Wennhold (2), O.A. Cornely (1), M. Bergwelt-Baildon (4), H.A. Schloesser (2)

Authors Affiliations(s): (1) University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Germany, (2) Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Germany, (3) Wisplinghoff Laboratories, Germany, (4) Department of Medicine III, University Hospital, LMU Munich, Germany

Background:

Recently published in vitro and in vivo studies imply that strengthening host immunity may improve outcome in invasive fungal infections (IFI). Preclinical and clinical investigations suggest a potential benefit of checkpoint inhibition in IFI and particularly in candidiasis. We here report our findings of comprehensive prospective phenotyping of circulating lymphocytes in patients with invasive candidiasis (IC) by Candida albicans.

Methods:

Patients (n=21) with IC, including candidemia, were included. Peripheral blood mononuclear cells (PBMCs) and serum samples of healthy controls (n=20) as well as PBMC and tumour-infiltrating lymphocytes (TILs) obtained from colorectal (n=6) and non-small cell lung (n=8) cancer patients served as control populations. Type and differentiation states of lymphocytes and the expression of 30 immune-regulatory molecules in PBMCs and TILs of study subjects were analysed by flow cytometry. Candida albicans specific cellular and humoral responses were assessed by fluorospot and antibody measurement, respectively.

Results:

Fractions and phenotypes of lymphocyte subsets in PBMC of IC patients were similar compared to PBMC controls, while they were different in TILs. PBMCs of patients with IC but not CA showed increased expression of immune-checkpoint molecules, which paralleled TILs (Figure 1). Expression patterns of co-inhibitory molecules were similar in IC PBMCs and TILs. Expression of PD-1 and TIGIT was higher in patients that died and fluorospot analysis of three representative IC patients showed a Candida-specific IL-2 response in one patient, which was enhanced using nivolumab in vitro (Figure 2).

Conclusions:

The expression patterns and the similarities between IC PBMCs and TILs implies a potentially beneficial effect of immune-checkpoint inhibition in IC patients. Together with robust preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment.



COI Institutional Grants: Yes
T cells of invasive candidiasis patients show patterns of T cell exhaustion suggesting checkpoint blockade as treatment option
Dr. Sibylle Mellinghoff
Dr. Sibylle Mellinghoff
ESCMID eAcademy. Mellinghoff S. 07/09/2021; 329542; 3779
user
Dr. Sibylle Mellinghoff
Abstract
Discussion Forum (0)
Abstract number: 3779

Session Type: ePosters

Session Title: ePosters

Authors(s): S. Mellinghoff (1), M. Thelen (2), M. Garcia-Marquez (2), P. Hartmann (3), J. Lehmann (2), N. Angela (3), J. Stemler (1), K. Wennhold (2), O.A. Cornely (1), M. Bergwelt-Baildon (4), H.A. Schloesser (2)

Authors Affiliations(s): (1) University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Germany, (2) Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Germany, (3) Wisplinghoff Laboratories, Germany, (4) Department of Medicine III, University Hospital, LMU Munich, Germany

Background:

Recently published in vitro and in vivo studies imply that strengthening host immunity may improve outcome in invasive fungal infections (IFI). Preclinical and clinical investigations suggest a potential benefit of checkpoint inhibition in IFI and particularly in candidiasis. We here report our findings of comprehensive prospective phenotyping of circulating lymphocytes in patients with invasive candidiasis (IC) by Candida albicans.

Methods:

Patients (n=21) with IC, including candidemia, were included. Peripheral blood mononuclear cells (PBMCs) and serum samples of healthy controls (n=20) as well as PBMC and tumour-infiltrating lymphocytes (TILs) obtained from colorectal (n=6) and non-small cell lung (n=8) cancer patients served as control populations. Type and differentiation states of lymphocytes and the expression of 30 immune-regulatory molecules in PBMCs and TILs of study subjects were analysed by flow cytometry. Candida albicans specific cellular and humoral responses were assessed by fluorospot and antibody measurement, respectively.

Results:

Fractions and phenotypes of lymphocyte subsets in PBMC of IC patients were similar compared to PBMC controls, while they were different in TILs. PBMCs of patients with IC but not CA showed increased expression of immune-checkpoint molecules, which paralleled TILs (Figure 1). Expression patterns of co-inhibitory molecules were similar in IC PBMCs and TILs. Expression of PD-1 and TIGIT was higher in patients that died and fluorospot analysis of three representative IC patients showed a Candida-specific IL-2 response in one patient, which was enhanced using nivolumab in vitro (Figure 2).

Conclusions:

The expression patterns and the similarities between IC PBMCs and TILs implies a potentially beneficial effect of immune-checkpoint inhibition in IC patients. Together with robust preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment.



COI Institutional Grants: Yes
Abstract number: 3779

Session Type: ePosters

Session Title: ePosters

Authors(s): S. Mellinghoff (1), M. Thelen (2), M. Garcia-Marquez (2), P. Hartmann (3), J. Lehmann (2), N. Angela (3), J. Stemler (1), K. Wennhold (2), O.A. Cornely (1), M. Bergwelt-Baildon (4), H.A. Schloesser (2)

Authors Affiliations(s): (1) University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Germany, (2) Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Germany, (3) Wisplinghoff Laboratories, Germany, (4) Department of Medicine III, University Hospital, LMU Munich, Germany

Background:

Recently published in vitro and in vivo studies imply that strengthening host immunity may improve outcome in invasive fungal infections (IFI). Preclinical and clinical investigations suggest a potential benefit of checkpoint inhibition in IFI and particularly in candidiasis. We here report our findings of comprehensive prospective phenotyping of circulating lymphocytes in patients with invasive candidiasis (IC) by Candida albicans.

Methods:

Patients (n=21) with IC, including candidemia, were included. Peripheral blood mononuclear cells (PBMCs) and serum samples of healthy controls (n=20) as well as PBMC and tumour-infiltrating lymphocytes (TILs) obtained from colorectal (n=6) and non-small cell lung (n=8) cancer patients served as control populations. Type and differentiation states of lymphocytes and the expression of 30 immune-regulatory molecules in PBMCs and TILs of study subjects were analysed by flow cytometry. Candida albicans specific cellular and humoral responses were assessed by fluorospot and antibody measurement, respectively.

Results:

Fractions and phenotypes of lymphocyte subsets in PBMC of IC patients were similar compared to PBMC controls, while they were different in TILs. PBMCs of patients with IC but not CA showed increased expression of immune-checkpoint molecules, which paralleled TILs (Figure 1). Expression patterns of co-inhibitory molecules were similar in IC PBMCs and TILs. Expression of PD-1 and TIGIT was higher in patients that died and fluorospot analysis of three representative IC patients showed a Candida-specific IL-2 response in one patient, which was enhanced using nivolumab in vitro (Figure 2).

Conclusions:

The expression patterns and the similarities between IC PBMCs and TILs implies a potentially beneficial effect of immune-checkpoint inhibition in IC patients. Together with robust preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment.



COI Institutional Grants: Yes

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