Regression of feline sarcoma virus-induced sarcomas in dogs. II. Immunologic investigations

The serial development of cell-mediated immunity (CMI), cytotoxic antibody activity, serum blocking activity, and virus-neutralizing antibody levels were monitored in vitro for beagle and mongrel puppies inoculated with feline sarcoma virus (FeSV) and were compared to in vivo histologic markers of regression of induced sarcomas. CMI developed rapidly and maintained a high level of in vitro activity throughout the tumor life-span. Cytotoxic antibody levels similarly rose rapidly to peak just before clinically detectable regression and then declined during most of the regression sequence. This suggested antibody fixation at the tumor site, correlating with the histologic finding of focal necrosis and neutrophilic infiltrates. Inactivation of antibody by circulating antigen with subsequent immune complex formation was a possibility. Levels of virus-neutralizing antibody in sera paralleled those of cytotoxic antibody; their relationship in the circulation was not clear, but each related to virus-determined antigenic specificities. Serum blocking activity rose rapidly, leveled off during most of the tumor life-span, and rose slightly during the last stages of regression. This partly explained the lack of in vivo tumor lymphoid infiltrates to correlate with the striking in vitro CMI. Blocking activity was also present, however, when lymphoid infiltrates were seen histologically. Thus in vitro-in vivo correlation was best for cytotoxic antibody, which suggested that antigen-antibody reactions involving neutrophil-mediated regression sequences were important in effecting tumor-cell destruction.