Paclitaxel inhibits natural killer cell binding to target cells by down-regulating adhesion molecule expression.
BACKGROUND
Chemotherapy with paclitaxel is associated with impaired natural killer (NK) cell function. The purpose of this study was to determine the effect of paclitaxel treatment on NK cell adherence to target cells.


METHODS
Human NK-like YT cells or NK-sensitive K562 cells were exposed to submaximal cytotoxic concentrations (EC10 and EC30) of paclitaxel. The ability of surviving YT or K562 cells to adhere to untreated K562 cells or YT cells, respectively, was assessed in a conjugation assay. The effect of paclitaxel on adhesion molecule expression was determined by flow cytometry.


RESULTS
Paclitaxel treatment resulted in decreased conjugate formation, as well as decreased alpha4, alphaL, and beta7 integrin expression by YT cells and decreased ICAM-1 expression by K562 cells.


CONCLUSIONS
Paclitaxel inhibition of adhesion molecule expression resulted in impaired NK cell binding to target cells, which may have a negative impact on immune surveillance.
Loubani
Osama
O
Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
Hoskin
David W
DW
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D017239:Paclitaxel