Immune Selection of Tumor Cell Variants in Chickens Bearing Tumors Induced by Avian Sarcoma Virus¹

We have compared avian sarcoma cells, cultured from tumors at various stages of growth, in terms of their ability to synthesize infectious progeny virus and to express antigens that are reactive with the sensitized lymphocytes of tumorbearing hosts. Cell-mediated immunity in chickens bearing tumors induced by avian sarcoma viruses was monitored by each of a target cell cytotoxicity test and an antigen-driven lymphocyte stimulation assay. Our results show that it is only those tumor cells which have been derived from progressively growing neoplasms that are able to synthesize infectious progeny virus and to specifically interact with the sensitized lymphocytes of tumor-bearing hosts. In contrast, cells from regressing tumors do not express relevant antigens to the same extent as do progressors, and they synthesize noninfectious particles only. Experiments on cellular outgrowths, derived from the plating at limited dilution of progressively growing tumor cells, revealed that such producers of defective virus are present at the earliest stages of tumor growth. Both these cells and regressing tumor cells are poorly stained (about 10%) in indirect immunofluorescence tests by antiserum against viral envelope glycoprotein, whereas tumor cells from progressing neoplasms react well (about 60 to 85%). These results suggest that tumor cells which are found in regressing neoplasms are selected out by a functional immune response directed against cells which are efficient producers of progeny virus.