Impairment of natural killer functions by interleukin 6 increases lymphoblastoid cell tumorigenicity in athymic mice.
Expression of the human IL-6 gene in EBV-immortalized normal human B lymphocytes following retroviral-mediated transduction rendered these cells highly tumorigenic in athymic mice. The tumors were lymphomas composed of the originally inoculated human lymphoblastoid cells. Co-injection of IL-6 expressing EBV-immortalized cells with IL-6 nonexpressing control cells resulted in increased tumorigenicity of the IL-6 nonexpressing cells. The lymphoblastoid cells expressing IL-6 were indistinguishable from parental cell lines in morphology and in a variety of cell surface characteristics, and did not exhibit growth advantage over parental cell lines in vitro, such that increased tumorigenicity is unlikely to depend upon a direct oncogenic effect of IL-6 on the B cells. Rather, at high concentrations, IL-6 markedly inhibits human lymphoblastoid cell killing by IL-2-activated murine splenocytes in vitro, suggesting that IL-6-related tumorigenicity might depend upon IL-6 inhibiting cytotoxicity at the tumor site. Thus, production of IL-6 by tumor cells that results in natural killer cell dysfunctions illustrates a novel mechanism of tumor cell escape from immune surveillance.
Tanner
J
J
Laboratory of Immunology, Center for Biologics Evaluation and Research, Bethesda, Maryland 20892.
Tosato
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002472:Cell Transformation, Viral; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D004854:Herpesvirus 4, Human; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000209:etiology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D014162:Transfection
D006684:HLA-DR Antigens; D015850:Interleukin-6