title: The tumorigenicity of IL-2 gene-transfected murine M-3D melanoma cells is determined by the magnitude and quality of the host defense reaction: NK cells play a major role.
abstract: Transfection of a variety of tumor lines with the IL-2 gene strongly reduces their tumorigenic potential when applied to either euthymic or athymic animals. To elucidate the mechanisms underlying this phenomenon, we inoculated IL-2-transfected M-3D melanoma (M-3D-IL-2) cells into DBA/2 mice immunosuppressed by gamma-irradiation. Animals thus treated developed pigmented tumors, suggesting that IL-2 transfection of melanoma cells, instead of altering their neoplastic growth properties, renders them capable of evoking a tumoricidal host response. To define the critical effector cell, we injected M-3D-IL-2 and, for control purposes, nontransfected M-3D cells into DBA/2 recipients and analyzed the injection site. We found that 1) IL-2-expressing M-3D cells induce a much stronger inflammatory reaction than wild-type cells, 2) in both instances the infiltrate consists mainly of macrophages (40-60%) and granulocytes (30-40%), and 3) only the infiltrate of M-3D-IL-2 cell deposits contains a minor fraction of NK cells (approximately 1-2%). When we reconstituted sublethally irradiated animals with various leukocyte subsets, we found that unfractionated as well as macrophage-depleted peritoneal lavage cells but not NK cell-depleted peritoneal lavage cells were able to suppress the growth of IL-2-expressing M-3D cells. In vivo leukocyte depletion experiments showed that the NK cell-depleting asialo-GM1 antiserum, but not anti-macrophage and/or anti-granulocyte reagents, restored the tumorigenicity of M-3D-IL-2 cells. Our results indicate that the inflammatory tissue response evoked by IL-2-transfected cancer cells includes the attraction and/or activation of NK cells and that, in the experimental system used, these cells are critically needed for successfully controlling cancer growth in vivo.
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Schneeberger
authors.forename: F
authors.initials: F
authors.lastname: Koszik
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
authors.forename: R
authors.initials: R
authors.lastname: Kutil
authors.forename: G
authors.initials: G
authors.lastname: Stingl
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000528:radiation effects; D008545:Melanoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011828:Radiation Chimera / Q000276:immunology; D014162:Transfection / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2