| Description |
Tumors, regardless of their etiology, appear to express both unique tumor specific transplantation antigens (TSTA) and shared tumor associated antigens (TAA). Both known types of tumor antigens are capable of eliciting a variety of immune responses within the autochthonous host, as well as in the secondary syngeneic recipient of a tumor transplant. Therefore, it appears that the acceptance or rejection of tumor depends on whether a dominant effector or immuno-regulatory response persists within the tumor bearing host. It has been observed that the majority of ultraviolet light (UV)-induced tumors express TSTA determinants which function as strong rejection antigens when these tumors are transplanted into normal secondary syngeneic hosts. However, these same tumors are capable or progressive growth when implanted into a syngeneic host which possesses a population of UV-induced suppressor T-lymphocytes (Ts-cells) whose functional specificity appears to be directed toward TAA determinants. Evidence presented within this dissertation demonstrates that the effector-cells which mediate a state of TSTA specific UV-tumor immunity are T-lymphocytes that appear to lack demonstrable Ia determinants. On the other hand, the UV-induced immuno-regulatory cells, previously determined to be T-lymphocytes, are shown to be Ia positive and functionally radiosensitive. In addition, it is suggested that UV-damaged skin cells may express antigens which elicit this observed immuno-regulatory response. In contrast to UV-induced tumors, the majority of tumors induced by the chemical carcinogen methylcholanthrene (MCA) are capable of progressive growth when implanted into secondary syngeneic hosts. Upon transplantation into normal syngeneic hosts the immuno-potent TSTA determinants expressed by these tumors appear to elicit a dominant immuno-regulatory response. However, under the appropriate conditions both the TSTA and TAA determinants of MCA-tumors are capable of functioning as rejection antigens. In light of this immunogenic disparity which exists between UV and MCA tumors it is proposed that the immunogenic properties of a tumor may actually reflect the immunologic status of the primary host at the time that particular tumor emerged. Evidence supporting such a concept comes from the observation that, in addition to reduced latency periods for tumors induced by known chemical carcinogens in mice pretreated with UV, the secondary growth characteristics of MCA-tumors generated within these hosts is dissimilar to those in MCA-tumors generated within normal mice. Like UV-tumors, a high proportion of the MCA-tumors induced in UV-treated mice require the presence of UV-induced Ts-cells to maintain progressive growth within a syngeneic host. Furthermore, it is demonstrated that within hosts possessing distinct immunologic potentials, the immuno-potency of various tumor antigens, in regard to their ability to elicit an immuno-regulatory response, can be modulated. The evidence presented suggests that a preexisting Ts-cell population with TAA specificity is capable of shifting the relationship in immuno-potency between the TSTA and TAA determinants which are recognized by the host. From these observations it is concluded that the immunologic mechanisms which allow for emergence and progressive tumor growth within the autochthonous host may differ from those which function within a normal syngeneic host implanted with that same tumor. In addition to a discussion of various immunologic relationships between tumors and their hosts, a syngeneic tumor model system is proposed which could allow for the identification of specific immuno-regulatory mechanisms which may function within the autochthonous host during tumor emergence. |
