Development of host immunity to phenotypically diverse B16 melanoma clones. Implications for tumor growth and metastasis.

A B16 melanoma clone and four derived subclones exhibiting markedly different tumorigenic and metastatic potentials in young C57BL/6 mice were investigated comparatively to determine relative immunogenicities and capacities to induce humoral and cell-mediated immune responses following subcutaneous injection. All five populations stimulated some production of circulating antibody to a cell surface antigen complex (B16-gp70/80/85) specified by endogenous murine leukemia virus, as well as spleen-cell-mediated cytolytic and cytostatic activity apparently directed to the same antigens, but to varying extents. Immunogenicity and relative capacity to induce immunity were inversely related to tumorigenicity and tumor growth rate but were not obviously correlated with metastatic behavior. There were indications that tumor behavior might be influenced by developing or naturally acquired host immunity. The most rapidly growing clone, G3.26, which was poorly immunogenic and nonmetastatic in young mice, grew more slowly and was markedly metastatic in normal-aged mice in which some natural humoral and cellular responses cross-reactive with B16-gp70/80/85 antigens were detected. Furthermore, the highly immunogenic and normally nonmetastatic clone, G3.15, was appreciably metastatic in mice immunosuppressed by T lymphocyte depletion. In other cases, however, tumor behavior in immunosuppressed and immunopotentiated mice did not consistently indicate a critical role for host immunity in determining metastatic or nonmetastatic activity.