The effect of different anesthetics on tumor cytotoxicity by natural killer cells

Abstract

A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/ metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anesthetics-based general anesthesia. However, the underlying mechanism is yet to be determined. Because natural killer (NK) cells are implicated as important immune cells for tumor recurrence/ metastasis in the perioperative period, we examined the effect of different anesthetics on NK cell-mediated tumor cytotoxicity. Because adhesion molecule leukocyte function-associated antigen-1 (LFA-1) is functionally important in NK cells and is inhibited by commonly used volatile anesthetics isoflurane and sevoflurane, we hypothesized that these anesthetics would attenuate NK cell-mediated cytotoxicity. Using human NK cell line NK92-MI cells and tumor cell line K562 cells as a model system, we performed cytotoxicity, proliferation, conjugation and degranulation assays. Lytic granule polarization was also assessed. We showed that isoflurane, sevoflurane and LFA-1 inhibitor BIRT377 attenuated cytotoxicity, and reduced conjugation and polarization, but not degranulation of NK cells. Our data suggest that isoflurane and sevoflurane attenuated NK cell-mediated cytotoxicity at least partly by their LFA-1 inhibition in vitro. Whether or not isoflurane and sevoflurane attenuate NK cell-mediated tumor cytotoxicity in patients needs to be determined in the future.

Role of Sevoflurane on Natural Killer Group 2, Member D-Mediated Immune Response in Non-Small-Cell Lung Cancer: An In Vitro Study

“…In addition, Cho et al [ 25 ] demonstrated that the cytotoxicity of NK cells decreased postoperatively in patients who received sevoflurane-remifentanil. In the present study, the suppression of NK cell-mediated cytotoxicity by sevoflurane is consistent with the results of previous studies [ 23 – 25 ]; however, the research on the effects of sevoflurane on the expression of NK cell ligands remains scarce, which necessitates further evaluation of this field.…”

“…Previous research demonstrated that sevoflurane directly inhibits NK cell activity [ 23 – 25 ]. Tazawa et al [ 23 ] found that sevoflurane attenuated NK cell-mediated conjugation, polarization, and cytotoxicity by inhibiting leukocyte function-associated antigen-1 in NK cells.…”

“…Previous research demonstrated that sevoflurane directly inhibits NK cell activity [ 23 – 25 ]. Tazawa et al [ 23 ] found that sevoflurane attenuated NK cell-mediated conjugation, polarization, and cytotoxicity by inhibiting leukocyte function-associated antigen-1 in NK cells. Furthermore, in a randomized controlled trial to study the effect of anesthetic techniques on human NK cell function and cytotoxicity, Buckley et al [ 24 ] found that, in contrast to the serum from patients with propofol-paravertebral block, the serum from the patients with sevoflurane-opioid anesthesia downregulated the expression of NK cell-activating receptor CD16, reduced NK cell cytokine interleukin (IL)-1β and IL-10, and suppressed NK cell-mediated cell death against breast cancer cells.…”

Impact of anesthesia and analgesia techniques on glioblastoma progression. A narrative review

“… 30 A decreased expression of the adhesion molecule leukocyte-associated antigen-1 has been proposed as one of the mechanisms by which isoflurane and sevoflurane suppress the function of NK cells. 31 In contrast, propofol can stimulate the function of NK cells by increasing the expression of granzime B and IFNγ activating surface receptors (CD16, NKp30, NKp44, and NKG2D), and inhibiting prostaglandin E2 formation. 32–34 It is worth considering that the immunomodulatory effects of general anesthetics have been evaluated in vitro in NK cells; therefore, it remains to be determined whether the function of NK cells and lymphocytes is altered in the GBM microenvironment in vivo.…”

The Un(f)told Story of General Anesthesia

“…Isoflurane upregulates hypoxia‐inducible factor‐1 (HIF‐1), the overexpression of which is heavily implicated in tumorigenesis, cancer‐cell invasion, and poor survival outcomes . In cell cultures, isoflurane and sevoflurane have been shown to impair natural killer cell‐mediated cytotoxicity, which is critical to minimize postresection tumor recurrence . In addition, isoflurane has also been shown to promote the malignant potential of lung cancer and glioblastoma stem cells…”