Many studies have demonstrated that some individuals display an efficient immune response against resident tumor cells. In many cases such a response can be shown to effectively reject a tumor. Studies from this laboratory have demonstrated that the ability to reject a particular tumor (402AX teratocarcinoma) is under genetic control in mice, and that rejection is accomplished by the resistant individual's immune system. The goal of the studies proposed in this application is to define the differences between mice susceptible to the 402AX tumor. Initial studies have indicated that resistant mice have the capability to induce the expression of particular molecules on the tumor cells (major histocompatibility complex (MHC) antigens) and that these molecules are subsequently used by the host's immune system to recognize and reject the resident tumor cells. The resistant mouse, therefore, can manipulate its tumor cells such that they display molecules that are used to reject the tumor, while the susceptible mouse has no capability to modulate tumor cell molecule expression. The present experiments are aimed at understanding the mechanism(s) by which the resistant mouse induces expression of these MHC antigens. An understanding of this phenomenon would further define why certain individuals are susceptible to tumors while other individuals are resistant to tumors. In addition, once the mechanism of regulation is understood, one would have the information with which to convert susceptible individuals to resistant individuals.
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