Cytokine effects and role of adhesive proteins and Fc receptors in human macrophage-mediated antibody dependent cellular cytotoxicity.
Mononuclear phagocytes participate in host immunological defense against tumors. We have investigated the role of selected recombinant cytokines on human macrophage-mediated tumor cytotoxicity in vitro utilizing a human colon cancer cell line target, SW1116, and murine monoclonal antibody 17-1A. Blood monocytes were kept in continuous culture to allow differentiation into macrophages. Maximum antibody dependent cellular cytotoxicity (ADCC) as measured in a 3H-thymidine release assay occurred after culturing the monocytes for 5-7 days. Human recombinant macrophage colony stimulating factor (CSF) (1,000 U/ml) did not increase ADCC above control levels whereas recombinant human granulocyte-macrophage colony stimulating factor, interleukin 4, and interleukin 3 were all capable of increasing ADCC. Antibodies to the CD11/CD18 integrin receptors did not significantly inhibit ADCC. When the ADCC incubation occurred in the presence of antibodies to the human Fc receptors, ADCC was inhibited significantly only by anti-FcRIII (3G8). A role for tumor necrosis factor alpha or other soluble mediators of cytotoxicity was not demonstrable in this system. These studies suggest avenues for manipulation and augmentation of macrophage-mediated antitumor ADCC.
Department of Medicine, University of Rochester School of Medicine, New York.
J L
JL
Liesveld
K E
KE
Frediani
J M
JM
Winslow
R E
RE
Duerst
C N
CN
Abboud
D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002454:Cell Differentiation; D003115:Colony-Stimulating Factors / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000166:cytology; D009500:Neutralization Tests; D011961:Receptors, Fc / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D003115:Colony-Stimulating Factors; D016207:Cytokines; D007377:Interleukin-3; D011961:Receptors, Fc; D015847:Interleukin-4