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Natural Killer Cell Line NK-92-Mediated Damage of Medically Important Fungi
Stanislaw Schmidt1, Marie Luckowitsch1, Michael Hogardt2
1Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany.
Abstract:
Invasive fungal disease (IFD) in hematopoietic stem cell transplantation is associated with high morbidity and mortality. As the antifungal host response determines risk and outcome of IFD, there is growing interest in adoptive immunotherapy using T cells or natural killer (NK) cells. Although the NK-92 cell line has been tested as anticancer therapy in clinical trials, data on the antifungal activity of NK-92 cells are lacking. Here, we show that the NK-92 cell line exhibits considerable fungal damage on all medically important fungi tested, such as different species of Aspergillus, Candida, mucormycetes, and Fusarium. The extent of fungal damage differs across various species of mucormycetes and Fusarium, whereas it is comparable across different species of Aspergillus and Candida. Interferon (IFN)-γ levels in the supernatant were lower when NK-92 cells are co-incubated with Aspergillus fumigatus, Candida albicans, or Rhizopus arrhizus compared to the levels when NK-92 cells are incubated alone. Different to primary human NK cells, no increase of perforin levels in the supernatant was observed when the fungi were added to NK-92 cells. Our in vitro data demonstrated that the NK-92 cell line could be a feasible tool for antifungal immunotherapy, but data of animal models are warranted prior to clinical trials.
Insights
The NK-92 cell line shows antifungal activity against medically important fungi, suggesting potential for adoptive immunotherapy in hematopoietic stem cell transplantation patients. Further animal studies are needed before clinical trials.
Area of Science:
- Immunology
- Mycology
- Hematology
Background:
- Invasive fungal disease (IFD) poses significant risks in hematopoietic stem cell transplantation (HSCT).
- Antifungal host response is critical for IFD outcomes, driving interest in immunotherapy.
- Natural killer (NK) cells are explored for adoptive immunotherapy, but NK-92 cell antifungal data are limited.
Purpose of the Study:
- To evaluate the antifungal activity of the NK-92 cell line in vitro.
- To assess the potential of NK-92 cells as a tool for antifungal immunotherapy.
Main Methods:
- In vitro co-incubation of NK-92 cells with medically important fungi (Aspergillus, Candida, mucormycetes, Fusarium).
- Measurement of fungal damage.
- Quantification of cytokine (IFN-γ) and cytotoxic effector (perforin) levels in supernatants.
Main Results:
- NK-92 cells demonstrated considerable damage to all tested fungal species.
- Fungal damage varied among mucormycetes and Fusarium species but was consistent for Aspergillus and Candida.
- Lower IFN-γ levels were observed when NK-92 cells were co-incubated with certain fungi.
- Unlike primary NK cells, NK-92 cells did not show increased perforin levels upon fungal exposure.
Conclusions:
- The NK-92 cell line exhibits promising in vitro antifungal activity.
- NK-92 cells represent a potential candidate for developing antifungal immunotherapy.
- Further investigation in animal models is necessary to validate these findings before human clinical trials.
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