Surgical stress impairs natural killer cell programming of tumor for lysis in patients with sarcomas and other solid tumors.
BACKGROUND
Natural killer (NK) cells may provide a first line of defense against the metastatic implantation of circulating tumor emboli. Because tumor emboli are discharged systemically in patients undergoing solid tumor resection, it is important to determine the nature of surgical-stress impairment of perioperative NK cell cytotoxic function.


METHODS
The authors studied 85 patients undergoing surgical resection of solid tumors, most of whom had an abrupt and marked decrease in NK cell cytotoxicity that was detectable within 18 hours of surgical resection.


RESULTS
This impairment was not caused by rapidly emerging suppressor cells (measured in autologous effector cell mixing studies) or decreased NK cell frequency in the peripheral blood (assessed phenotypically and morphologically). Instead, surgical stress exerted a direct "toxic" effect on NK cells that could be localized to a specific phase of the NK cell tumor lysis cycle. Tumor binding and the first round of tumor lysis were intact postoperatively (measured in single-cell assays). However, postbinding programming for lysis was decreased sharply after surgery (assessed by calcium pulse assays). In addition, the kinetics of lysis and the rate of lytic programming were slower after surgery (assayed in target saturation kinetic chromium-51 release tests).


CONCLUSIONS
These latter defects probably were related to the programming for lysis deficiency because postprogramming NK cell maximal recycling capacity was not affected by surgical stress.
Pollock
R E
RE
Department of General Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Lotzová
E
E
Stanford
S D
SD
D002469:Cell Separation; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D010641:Phenotype; D013312:Stress, Physiological / Q000276:immunology*; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology