Rejection of Virus - Infected Tumors

The congenitally athymic nude mouse has been widely used to study the tumorigenicity of a variety of human and animal neoplasms (1-6). Yet, nude mice appear not to be totally immunodeficient; they do not have a higher incidence than normal mice of chemical carcinogenesis or spontaneous tumors and show infrequent metastases of tumors known to be metastatic in their original host (4, 7-10). Although growth in the nude mouse is a major criterion for tumorigenicity of pr imary or cultured cells (5, 6), it is increasingly clear that many tumors fail to grow in the nude mouse (4, 11), even though the basis for this discrimination between different tumors remains unclear. The present studies were initiated to develop an appropriate model system for defining both the mechanism of discrimination between different types of tumors, and the possible mechanisms available for tumor rejection in the nude mouse. For these studies, cell lines known to be highly tumorigenic in the nude mouse were modified by rendering them virus persistently infected (P.I.) 1 with a variety of RNA viruses. It will be demonst~'ated that most such P.I. tumor cells are effectively rejected by the nude mouse. We believe that the studies on the rejection of virus P.I. tumor cells by the nude mouse may provide useful insights into the immunological control of tumor cells having altered surface properties and into the mechanisms of resistance to persistent viral infections as well.