Discussion paper: specific paralysis of the antitumor cellular immune response produced by growing tumors studied with a radioisotope footpad assay.

The kinetics of the antitumor cellular immune response of mice with progressively growing syngeneic tumors were determined in vivo using a quantitative radioisotopic footpad assay. A close correlation was found between the size of the tumor and the degree of the cellular immune response. An initial phase of cellular immune stimulation was followed by specific suppression and subsequent immunologic paralysis as the tumor grew larger. This immune paralysis was attributed to increased tumor load since a homogenate of an SV40 transformed fibrosarcoma injected intraperitoneally into tumor-immune mice specifically depressed their cellular immune response. The fraction of the tumor homogenate that brought about this depression was present in the high speed supernatant and pellet of a 3M KCl extract of the tumor. The specificity of the depression was determined in vivo by the radioisotopic footpad assay and in vitro by a 51Cr cytolysis assay. Unwashed spleen cells harvested from mice bearing large tumors were unreactive in a local adoptive footpad assay. However, reactivity could be restored by repeatedly washing the spleen cells.