Juan P Cata1,2, Maria F Ramirez2,3, Jose F Velasquez2,4, A I Di5, Keyuri U Popat6, Vijaya Gottumukkala6,2, Dahlia M Black7, Valerae O Lewis8, Jean N Vauthey9. 1. Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. jcata@mdanderson.org. 2. Anesthesiology and Surgical Oncology Research Group, Houston, TX, U.S.A. 3. Department of Anesthesiology, Massachusetts General Hospital, Boston, MA, U.S.A. 4. University CES, School of Medicine, Medellin, Colombia. 5. Department of Pathology, Texas A&M Cancer Center, Baylor Scott & White Memorial Hospital, Temple, TX, U.S.A. 6. Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. 7. Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. 8. Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. 9. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A.
Abstract
BACKGROUND: One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery. MATERIALS AND METHODS: NK cells from healthy donors and 43 patients who had undergone surgery for cancer were isolated. The function of NK cells was measured by lactate dehydrogenase release assay. NK cells were incubated with clinically relevant concentrations of lidocaine. By flow cytometry, we determined the impact of lidocaine on the expression of galactosylgalactosylxylosylprotein3-beta-glucuronosytranferase 1, marker of cell maturation (CD57), killer cell lectin like receptor A, inhibitory (NKG2A) receptors and killer cell lectin like receptor D, activation (NKG2D) receptors of NK cells. Differences in expression at p<0.05 were considered statistically significant. RESULTS: Lidocaine increased the expression of NKG2D receptors and stimulated the function of NK cells against ovarian, pancreatic and ovarian cancer cell lines. Lidocaine also increased the cytolytic activity of NK cells from patients who underwent oncological surgery, except for those who had orthopedic procedures. CONCLUSION: Lidocaine showed an important stimulatory activity on NK cells. Our findings suggest that lidocaine might be used perioperatively to minimize the impact of surgery on NK cells. Copyright
BACKGROUND: One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery. MATERIALS AND METHODS: NK cells from healthy donors and 43 patients who had undergone surgery for cancer were isolated. The function of NK cells was measured by lactate dehydrogenase release assay. NK cells were incubated with clinically relevant concentrations of lidocaine. By flow cytometry, we determined the impact of lidocaine on the expression of galactosylgalactosylxylosylprotein3-beta-glucuronosytranferase 1, marker of cell maturation (CD57), killer cell lectin like receptor A, inhibitory (NKG2A) receptors and killer cell lectin like receptor D, activation (NKG2D) receptors of NK cells. Differences in expression at p<0.05 were considered statistically significant. RESULTS:Lidocaine increased the expression of NKG2D receptors and stimulated the function of NK cells against ovarian, pancreatic and ovarian cancer cell lines. Lidocaine also increased the cytolytic activity of NK cells from patients who underwent oncological surgery, except for those who had orthopedic procedures. CONCLUSION:Lidocaine showed an important stimulatory activity on NK cells. Our findings suggest that lidocaine might be used perioperatively to minimize the impact of surgery on NK cells. Copyright
Authors: Theresa K Leslie; Andrew D James; Fulvio Zaccagna; James T Grist; Surrin Deen; Aneurin Kennerley; Frank Riemer; Joshua D Kaggie; Ferdia A Gallagher; Fiona J Gilbert; William J Brackenbury Journal: Biochim Biophys Acta Rev Cancer Date: 2019-07-23 Impact factor: 10.680