Proceedings: Proposed mechanisms by which autochthonous neoplasms escape immune rejection.

Abstract

The available evidence suggests that both human and animal cancers are generally recognized by their hosts to be antigenic. Both antibody- and cell-mediated immune reactions have been reported to occur in response to tumor cells in cancer-bearing animals. One of the major unanswered questions in cancer immunology is why these immune responses do not lead to the successful destruction of the tumor. For this presentation we have collected data in the autochthonous SV40 hamster sarcoma model system that suggest that cell-mediated and humoral responses against SV40 tumor surface antigens appear early after infection of neonatal animals with this oncogenic virus. Cell-mediated immunity measured in vitro in the microcytotoxicity assay against SV40 tumor target cells was demonstrable throughout several months prior to tumor appearance and thereafter until the death of the animals. Antibody, cytostatic to the growth of SV40 tumor cells when measured in vitro and in vivo , appeared early after the initial transformed cells were present but could never be detected during the several weeks prior to the visible appearance of s.c. autochthonous tumors. Lymphocytes from animals bearing SV40 sarcomas, although cytotoxic in vitro , were generally incapable of conferring protection against SV40 tumor challenge to normal syngeneic recipients, suggesting some additional functional impairment of antitumor cytotoxicity in vivo . The data collectively suggest that, early after the appearance of SV40 neoplasms, antibody inhibitory to the growth of tumor cells appears but is not cytotoxic. This antibody functions by restricting the initial growth of the tumor cells and perhaps serves to diminish tumor cell antigenicity (afferent and efferent inhibition). Cell-mediated immunity appears somewhat later but is obviously ineffective in destroying the tumor focus, as it grows slowly over many months and eventually metastasizes. Inhibititor, presumably circulating antigen released from the enlarging tumor mass, binds to circulating lymphocytes and inhibits their cytotoxicity against the spreading tumor. Thus the growth of the SV40-transformed cells, comprising the initial tumor focus, to a lethal, spreading cancer is permitted to occur because of a series of blocking and inhibitory events involving antibody initially, possibly antigen and antibody intermediately, and primarily antigen in the later stages of tumor progression.