E1A oncogene induction of cytolytic susceptibility eliminates sarcoma cell tumorigenicity.

The manner in which oncogenes influence tumorigenicity beyond their ability to immortalize cells is uncertain. We tested the hypothesis that, in addition to subverting cellular growth controls, oncogenes can actively determine tumor-inducing capacity by affecting neoplastic cell susceptibility to destruction by the host cellular immune response. The adenovirus type 5 E1A oncogene, which induces susceptibility to lysis by natural killer cells and encodes epitopes recognized by cytotoxic T lymphocytes, was transfected into highly tumorigenic sarcoma cells. E1A expression in these sarcoma cells eliminated their tumorigenicity in recipients with natural killer cell activity that was competent to lyse these E1A-positive targets. Thymus-dependent responses were not required for tumor rejection. These results indicate that oncogene-regulated cellular pathways that affect neoplastic cell susceptibility to natural killer cell lytic mechanisms may influence tumor development in the immunocompetent host.