NK cells rapidly remove B16F10 tumor cells in a perforin and interferon-gamma independent manner in vivo.
Natural killer (NK) cells have been shown critical in reducing tumor lung metastasis in various murine cancer models. Effector molecules such as perforin and IFN-gamma may play important roles in inhibition of metastasis. However, most of these conclusions were based on experiments that involved quantitation of metastatic colonies several weeks after tumor challenge. The roles of NK cells and their effector molecules (perforin and IFN-gamma) in the initial immune responses against tumor metastasis in lungs are still unknown. By using the B16F10 melanoma tumor model combined with confocal microscopy, we observed an increase in numbers of B16F10 cells in NK-depleted mice at 60 min post tumor inoculation, but this effect was independent of perforin or IFN-gamma. In addition, NK cell numbers in lungs after tumor injection rapidly increased suggesting a redistribution of NK cells in the lungs. However, NK cells were not found in contact with tumor cells until day 6 or later. Our data indicate that during early responses against B16F10 cells, NK cells use another mechanism(s) besides perforin and IFN-gamma to prevent tumor metastasis.
Grundy
Martin A
MA
Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Building, One Medical Center Drive, Lebanon, NH 03756, USA.
Zhang
Tong
T
Sentman
Charles L
CL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D005456:Fluorescent Dyes / Q000032:analysis; D007157:Immunologic Surveillance; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008164:Luminescent Proteins / Q000032:analysis; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009368:Neoplasm Transplantation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D000097573:Red Fluorescent Protein
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D005456:Fluorescent Dyes; D007371:Interferon-gamma; D037181:Lectins, C-Type; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D000097573:Red Fluorescent Protein