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Updated: Aug 18, 2026
Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
A phagocytic cell line markedly improves survival of infected neutropenic mice
Brad J Spellberg1, Mary Collins, Samuel W French
1Los Angeles Biomedical Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. bspellberg@labiomed.org
Abstract:
Disseminated candidiasis is a frequent infection in neutropenic patients, in whom it causes 50% mortality, despite antifungal therapy. As the duration of neutropenia is the strongest predictor of survival in neutropenic patients with invasive fungal infections, neutrophil transfusions are a logical, therapeutic option. However, significant technical barriers have prevented the clinical use of neutrophil transfusions. To overcome these barriers, we identified a human phagocytic cell line that could be administered to candidemic hosts in lieu of freshly harvested neutrophils. HL-60 cells killed Candida albicans in vitro. Activation of HL-60 cells with dimethyl sulfoxide and retinoic acid abrogated the cells' proliferation and augmented their killing of C. albicans. Administration of activated HL-60 cells to candidemic, neutropenic mice significantly improved survival (53% vs. 0%). Live HL-60 cells chemotaxed to sites of infection, phagocytized C. albicans, and reduced the fungal burden in key target organs. Although unactivated HL-60 cells also reduced tissue fungal burden in vivo, they did not improve survival as a result of their toxicity in infected mice. In contrast, no toxicity as a result of activated HL-60 cells was observed at up to 2 months of follow-up. To our knowledge, this is the first description of a cell line-based immunotherapy for an infectious disease. With further refinements, activated HL-60 cells have the potential to overcome the technical barriers to neutrophil transfusions.
Insights
Activated HL-60 cells offer a potential cell line-based immunotherapy for disseminated candidiasis in neutropenic patients. This approach improved survival in mice by targeting Candida albicans infections, overcoming barriers to neutrophil transfusions.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Disseminated candidiasis presents a high mortality rate in neutropenic patients, often exceeding 50% despite antifungal treatments.
- Neutropenia duration is a critical factor for survival in invasive fungal infections, making neutrophil transfusions a logical but technically challenging therapeutic strategy.
Purpose of the Study:
- To identify and evaluate a cell line alternative to neutrophil transfusions for treating disseminated candidiasis.
- To assess the efficacy and safety of activated HL-60 cells as a cell-based immunotherapy against Candida albicans.
Main Methods:
- HL-60 cells were differentiated and activated using dimethyl sulfoxide and retinoic acid to enhance their phagocytic and fungicidal properties against Candida albicans.
- Activated HL-60 cells were administered to neutropenic mice infected with Candida albicans to evaluate survival rates and therapeutic effects.
- In vivo studies assessed HL-60 cell migration to infection sites, phagocytosis of Candida albicans, fungal burden reduction, and potential toxicity.
Main Results:
- Activated HL-60 cells demonstrated significant fungicidal activity against Candida albicans in vitro.
- Administration of activated HL-60 cells to candidemic, neutropenic mice resulted in a significant survival improvement (53% vs. 0%) compared to controls.
- Activated HL-60 cells effectively migrated to infection sites, phagocytosed Candida albicans, reduced fungal burden in organs, and showed no observed toxicity for up to two months.
Conclusions:
- Activated HL-60 cells represent a promising cell line-based immunotherapy for disseminated candidiasis, overcoming technical limitations of neutrophil transfusions.
- This novel approach has the potential to improve outcomes for neutropenic patients suffering from invasive fungal infections.
- Further research and refinement of activated HL-60 cell therapy could provide a viable alternative to traditional neutrophil transfusions.
