Tumor necrosis factor-mediated cytotoxicity by tumor-associated macrophages.
We have directly demonstrated that macrophages present within solid EMT6 mammary tumors (of BALB/c origin) produce TNF-alpha (TNF). These tumor-associated macrophages lysed WEHI-164, a TNF-sensitive cell line, very efficiently. This cytotoxicity was abrogated in the presence of anti-TNF antisera. In contrast, EMT6 cells, the tumor from which the macrophages were obtained, were not effectively lysed by the macrophages and were 100-fold less sensitive to lysis by recombinant mouse TNF. Thus, marked heterogeneity exists among tumors regarding sensitivity to TNF-mediated cytotoxicity. Similarly, macrophages which infiltrate into EMT6 multicellular spheroids implanted into the peritoneal cavity as well as free cells within the cavity exhibited TNF-mediated cytotoxicity of WEHI-164 cells, but failed to lyse EMT6 cells. The kinetics of lysis by these cells was similar to that of recombinant mouse TNF.
Wilson
K M
KM
Cancer Center, University of Rochester Medical Center, New York 14642.
Siegal
G
G
Lord
E M
EM
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity; D011994:Recombinant Proteins; D012513:Sarcoma, Experimental / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*
D007106:Immune Sera; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha