Neoantigen Expression in Chemical Carcinogenesis

Abstract

Neoplastic transformation induced by chemical carcinogens results in the expression in transformed cells of antigens which are not present in their normal counterparts, at least in the adult host. In the early studies with chemically induced tumors (Foley, 1953; Baldwin, 1955; Prehn and Main, 1957), neoantigens were defined by their capacity to elicit immunity to transplanted tumor and were termed “tumor-specific transplantation antigens.” It is now evident that immune responses are elicited against these antigens in the autochthonous host, and they must be viewed as a limiting (or enhancing) component of chemical carcinogenesis. It is therefore now appropriate to refer to these neoantigens, which are also viewed as components of the tumor cell surface membrane, as “tumor-associated rejection antigens.” Following the development of transplanted tumor models in syngeneic hosts for studying tumor immune mechanisms, in vitro methods have been introduced for detecting cellular and humoral responses to tumor-associated antigens. Techniques such as membrane immunofluorescence staining of viable tumor cells in suspension and in vitro assays of serum antibody and lymphocyte cytotoxicity against cultured tumor cells almost certainly are detecting antigens expressed at the cell surface. Moreover, the specificities of these reactions are often identical to those of the tumor rejection antigens. Even so, it is preferable to refer to the neoantigens detected by these in vitro techniques as “tumor-associated surface antigens,” since their identity to rejection antigens in most cases is not proven.