Anti-tumor Immune Responses of the Tumor-Bearing Host: The Case for Antibody-Mediated Immunologic Enhancement

Abstract

Analyses of host immune responses taking place during the growth from small inocula either as ascites or as solid subcutaneous tumors of a number of carcinogen-induced, immunogenic, murine tumors have shown that host immune responses are fully compatible with progressive tumor growth in their syngeneic hosts. Both B cell (antibody) and T cell ("killer cell") responses were detected in situ, and progressive tumor growth continued in concert with these responses. Tumor cells, after 2 weeks of growth in vivo, became resistant to the induced killer cells. The modulating agent appears to be anti-tumor antibody. The kinetics of the appearance of the antibody response and its specificity suggested that the responsible epitopes are uniquely expressed on tumor cells (oncotopes). Anti-oncotope antibody was found bound to these resistant tumor cells, yet the cells were fully capable of growing progressively, despite the presence of killer cells in their midst. These observations are compatible with data first reported 35 years ago suggesting that anti-tumor antibody promoted or enhanced tumor growth. Immunized mice have T-cytotoxic cells (CTL, MHCrestricted) in their spleens and lymph nodes, whereas the killer cells found in the ascites of tumor bearers were MHCunrestricted. In vivo grown tumor cells were completely resistant to spleen CTL of immune mice. The implications of these observations are of consequence not only in the design of effective immunotherapeutic protocols to eliminate cancer but also for a better understanding of self-tolerance, autoimmunity, and the genetics of the cancer formation. A unifying hypothesis is presented which explains how antibody-mediated immunologic enhancement is operative both in permitting progressive tumor growth and in allograft retention.