Comparison of antibody isotypes in sera and circulating immune complexes during tumor growth and metastasis of three tumor models in mice.

The sera and circulating immune complexes (CICs) from mice bearing either UV-2237 mm, K-1735 M2, or B16-BL6 were analyzed for antibody isotype distribution during primary tumor growth and spontaneous metastasis. These studies clearly demonstrate that elevated CIC concentrations parallel the initial stages of primary tumor growth; however, the CICs, as well as serum concentration of all immunoglobulin G isotypes, rapidly decrease to near normal levels in the presence of heavy tumor burden. Following resection of the primary footpad tumor, increases in CIC levels paralleled outgrowth of metastasis; however, the antibody content of the CICs was isotypically restricted to immunoglobulin G2b and immunoglobulin G3 regardless of the tumor type. The immunoglobulin G isotype content of the CICs did not correspond to elevations in the serum concentrations of each respective isotype during neither primary nor metastatic tumor growth. This serial study indicates that the use of non-antigen-specific assays for CICs without regard to tumor burden or possible antibody isotypic restriction may be misleading, and that CIC levels can indeed correlate with metastatic tumor burden.