Selection and rejection of retrovirus-expressing tumor cells from a heterogeneous murine leukemia virus-infected cell population.

We studied the basis of tumor recurrence at sites of rejection of retrovirus-infected guinea pig fibrosarcoma cells. Tumor recurrences, in contrast to the parent tumor, lacked retroviral antigens and did not release infectious virus. When reinjected into syngeneic animals, cell lines derived from tumor recurrences grew progressively. Tumor recurrences could be infected with the homologous retrovirus. Tumor rejection and recurrence were modulated by host immunity. In guinea pigs immunized to virus-infected cells, tumor recurrences occurred earlier and in a higher proportion of animals than in nonimmune guinea pigs. In some immunosuppressed guinea pigs, retrovirus-infected tumor cells grew progressively. Progressively growing tumors of immunosuppressed guinea pigs contained large amounts of infectious virus and expressed viral antigens. To identify the source of tumor recurrences, the parent virus-infected tumor was cloned. Clones were heterogeneous in virus expression; some clones released large quantities of infectious virus; others did not. Two clones formed tumors in syngeneic animals. Injection of a virus producer clone into virus-immune animals was not followed by tumor recurrence. The data suggest that the reappearance of tumors at sites of injection of retrovirus-infected fibrosarcoma cells represents immune selection and rejection of retrovirus-expressing cells. Cells with the potential to form tumor recurrences existed in the parent virus-infected tumor population.