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Updated: Mar 1, 2026

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Impact of Steroids on Natural Killer Cells Against Cytotoxicity and Hepatitis C Virus Replication
M Ohira1, S Nishida2, P Tryphonopoulos2
1Department of Surgery, Division of Liver and Gastrointestinal Transplantation, University of Miami Miller School of Medicine, Miami, Florida; Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
Background:
Natural killer (NK) cells play important roles in killing tumor and virus-infected cells. Immunosuppression used after organ transplantation is thought to increase the risk of tumor recurrence and viral infections. However, the effect of immunosuppressive drugs on NK cells has not yet been clearly established. Therefore, we examined the effect of immunosuppression on NK cells.
Methods:
NK cells were cultured for 7 days in the presence of interleukin-2 (100 U/mL) with or without the following immunosuppressive drugs: tacrolimus, cyclosporine A, corticosteroid (methylprednisolone [MP]), mycophenolate mofetil, and rapamycin. The effect of the drugs on NK cell activation was tested on the basis of the following: NK cell phenotype, NK cell proliferation, cytotoxicity against K562 cells, cytokine production by NK cells, and anti-hepatitis C virus (HCV) activity with HCV genomic replicon cells.
Results:
NK cells showed relatively robust functions in the presence of tacrolimus and cyclosporine A. Mycophenolate mofetil and rapamycin significantly prevented only NK cell proliferation (P < .05). In contrast, MP significantly inhibited the proliferation, cytotoxicity, and anti-HCV effect (10.9%, 18.5%, and 1.9%, respectively) of NK cells. Furthermore, MP specifically inhibited the expression of NK cell activation markers and the production of interferon-γ (P < .05).
Conclusions:
Corticosteroids have distinct effects on NK cells, which may have important implications for NK cell function in cytotoxicity and HCV effect after transplantation.
Insights
Immunosuppressive drugs impact natural killer (NK) cell functions. Corticosteroids significantly inhibit NK cell proliferation, cytotoxicity, and anti-hepatitis C virus (HCV) activity, unlike other tested immunosuppressants.
Area of Science:
- Immunology
- Transplantation Medicine
- Virology
Background:
- Natural killer (NK) cells are crucial for eliminating tumor and virus-infected cells.
- Immunosuppression post-transplantation may increase risks of tumor recurrence and viral infections.
- The precise impact of immunosuppressive drugs on NK cell function remains unclear.
Purpose of the Study:
- To investigate the effects of common immunosuppressive drugs on NK cell functions.
- To determine how immunosuppression influences NK cell-mediated anti-tumor and anti-viral activities.
Main Methods:
- NK cells were cultured with interleukin-2 and various immunosuppressive drugs (tacrolimus, cyclosporine A, methylprednisolone [MP], mycophenolate mofetil, rapamycin).
- Assessed NK cell phenotype, proliferation, cytotoxicity against K562 cells, cytokine production, and anti-hepatitis C virus (HCV) activity.
- Utilized HCV genomic replicon cells to evaluate anti-viral effects.
Main Results:
- Tacrolimus and cyclosporine A demonstrated minimal impact on NK cell functions.
- Mycophenolate mofetil and rapamycin primarily inhibited NK cell proliferation.
- Methylprednisolone (MP) significantly impaired NK cell proliferation, cytotoxicity, and anti-HCV activity, also reducing activation markers and interferon-γ production.
Conclusions:
- Corticosteroids, specifically MP, exert distinct and significant inhibitory effects on NK cell functions.
- These findings highlight the critical implications of corticosteroid use on NK cell-mediated cytotoxicity and anti-HCV responses in transplant recipients.
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