Docetaxel treatment of HT-29 colon carcinoma cells reinforces the adhesion and immunocytotoxicity of peripheral blood lymphocytes in vitro.
In vitro effects of docetaxel on the human colon carcinoma cell line HT-29 were studied with respect to the expression of different adhesion and surface marker molecules, the adhesion and immunocytotoxicity of peripheral blood lymphocytes and the secretion of IFN-gamma and TNF-alpha. Docetaxel, in a low concentration range (1-3x10-9 M), increased the expression of the adhesion molecules LFA-3, ICAM-1, CD44s, CD44v6, CD15, CD13 and VLA-4/5/6 on the tumor cells. Unstimulated and interleukin-2 (IL-2) activated killer (LAK) cells showed a better adherence to docetaxel treated HT-29 cells than to untreated cells. In neutralization experiments, anti-LFA-3, -CD44v6, -CD15, -VLA -4 and anti-CD13 mAb reduced the lymphocyte adhesion to untreated and docetaxel treated cells at different degrees, while CEA mAb increased the adhesion. Unstimulated and IL-2 activated lymphocytes exhibited significantly higher cytotoxicities against docetaxel treated cells than against untreated HT-29 cells. Unstimulated and IL-2 stimulated lymphocytes secreted more TNF-alpha and IFN-gamma when cocultured with docetaxel treated HT-29 cells than with untreated cells. These results suggest, that the increased lymphocyte mediated cytotoxicity against docetaxel treated HT-29 colon carcinoma cells may reflect an immunological process coupled with induction of differentiation, that may contribute to the clinically known cytostatic effects of the drug.
Grünberg
E
E
Institute of Pharmacy, Free University Berlin, Germany.
Eckert
K
K
Maurer
H R
HR
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D000077143:Docetaxel; D019073:HT29 Cells; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D043823:Taxoids
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000972:Antineoplastic Agents, Phytogenic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel