Interferon‐induced alterations in metastatic capacity, class‐1 antigen expression and natural killer cell sensitivity of melanoma cells

Abstract

Pre‐treatment of B16 melanoma cells with recombinant interferon‐γ (IFN‐γ) markedly increased their lung‐colonising capacity following i.v. injection into syngeneic mice as compared with control cells. A similar enhancement was observed following the injection of treated cells into athymic nude mice but not in athymic mice carrying the beige mutation. Pre‐treatment of syngeneic mice with anti‐asialo GM₁ antibody effectively abrogated any interferon‐induced increase in experimental metastatic activity. The same IFN‐γ treatment significantly increased resistance of B16 cells to splenic natural killer (NK) cell activity as determined by in vitro assays. IFN‐α/β pre‐treatment of B16 cells decreased sensitivity to NK‐cell‐mediated lysis to a lesser extent than IFN‐γ and had no detectable effect upon the subsequent metastatic activity of the tumour cells. Class‐1 antigen expression was altered by these IFN treatments, with IFN‐γ causing dramatic increases in expression of H‐2D^b antigen, in a pattern consistent with the possibility that increased H‐2 antigen expression on B16 cells led to decreased NK‐cell sensitivity which was reflected by an increase in experimental metastatic capacity.