Prognostic and pathogenetic implications of immune complexes in human cancer

The dynamic relationships of circulating immune complexes (CIC) and associated immune reactants to stage of disease and prognosis in cancer patients have been evaluated for malignant melanoma. Patients were divided into group I patients, with no evidence of disease at sample time; group II patients, with minimal tumor burden; and group III patients, with advanced metastatic disease. By means of single- and serial-sample determinations, we have demonstrated correlation of CIC concentration, size, and composition to tumor burden, disease progression, and high risk of disease recurrence. In view of the phenotypic heterogeneity of antigen expression in malignant melanoma, we have extracted, purified, and utilized melanoma-associated antigens (MAA) from CIC, and human oncofetal antigens (HOFA) from fetal liver cells, and reacted them with patients' sera in an in vitro model that simulates tumor burden changes. The observed changes in CIC concentration and lattice size upon reaction with MAA and HOFA demonstrated a significant (p less than or equal to 0.001) relationship to patients' in vivo tumor burden, as well as to the origin of serum and antigen involved. Our results suggest a homeostasis of CIC size and concentration to associated antibodies and antigens operational in malignant melanoma patients' sera. In addition, we have demonstrated how the monitoring of more than one immune reactant, characterization of CIC size and composition, and evaluation of resulting reequilibrium caused by in vitro addition of antigen or antibody, could allow for an improved assessment of humoral immunity and its related pathogenetic effects in cancer patients.