Author: Valérie Rössler-Fehr, et al.
Canadian Journal of Anesthesia. 2026;73:478–489.
Natural killer cells are an important component of the immune system’s defense against cancer. They recognize and destroy malignant cells by releasing cytotoxic substances, particularly perforin and granzyme. This laboratory study examined whether exposure to sevoflurane impairs the ability of natural killer cells to induce tumor-cell death.
Study Design
Researchers exposed a human natural killer cell line to 2.2% sevoflurane for two hours. The treated natural killer cells were then incubated with leukemia cells.
The investigators evaluated:
- Apoptosis of the leukemia cells
- Natural killer cell degranulation
- Cytokine messenger RNA production
- Extracellular vesicle size and concentration
- Perforin levels within natural killer cells and in the surrounding culture medium
Key Findings
After 24 hours of co-incubation, leukemia cells exposed to sevoflurane-treated natural killer cells demonstrated an average 36% reduction in early apoptosis.
This finding suggests that prior sevoflurane exposure temporarily impaired the ability of natural killer cells to destroy malignant cells.
Natural killer cell degranulation, cytokine messenger RNA production, and extracellular vesicle characteristics were not significantly changed by sevoflurane exposure.
However, perforin production was reduced. At 48 hours, both intracellular perforin and perforin released into the culture medium were approximately 16% lower in the sevoflurane-treated group.
Proposed Mechanism
Perforin creates pores in the membrane of a targeted tumor cell, allowing granzyme to enter and activate apoptosis.
The reduction in tumor-cell apoptosis observed after sevoflurane exposure appears to be related primarily to decreased perforin production rather than impaired natural killer cell degranulation or altered cytokine production.
The effect was described as transient, but it provides a possible biological mechanism through which volatile anesthetics might influence perioperative cancer immunity.
Clinical Implications
Clinical studies have raised concern that volatile anesthetics could be associated with less favorable cancer outcomes than intravenous anesthesia. Suppression of natural killer cell activity has been proposed as one possible explanation.
This study supports the biological plausibility of that concern by showing that sevoflurane can impair natural killer cell-mediated tumor-cell killing under laboratory conditions.
However, the findings do not demonstrate that sevoflurane increases cancer recurrence or reduces survival in surgical patients. An in vitro cell model cannot reproduce the complex immune, inflammatory, surgical, and tumor-related factors present in humans.
Therefore, this study should not by itself change anesthetic practice or establish total intravenous anesthesia as superior for cancer surgery.
Limitations
The experiment used a natural killer cell line and leukemia target cells rather than immune cells and solid tumors obtained directly from surgical patients.
The sevoflurane exposure occurred under controlled laboratory conditions and may not precisely represent clinical anesthesia. The study also evaluated cellular behavior rather than cancer recurrence, metastasis, or survival.
Further clinical research is required to determine whether these laboratory findings translate into meaningful differences in patient outcomes.
Conclusion
Exposure of natural killer cells to sevoflurane reduced their ability to induce early apoptosis in malignant cells. The impaired tumor-cell defense appeared to be associated with decreased perforin production.
These findings provide a potential mechanism for the suspected effects of volatile anesthetics on cancer immunity, but they remain laboratory observations and do not establish that sevoflurane worsens cancer outcomes in patients.
We thank the Canadian Journal of Anesthesia for allowing us to summarize this important clinical research.