Mechanisms of syngeneic tumor rejection. Susceptibility of host-selected progressor variants to various immunological effector cells.

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Abstract
The UV-induced fibrosarcoma 1591 generally is rejected by normal syngeneic mice and only rarely exhibits progressive growth. Five of these rare progressor tumors were isolated from normal animals to determine the selective pressures that had been exerted upon the parental tumor by normal immunocompetent hosts. The variant tumor cell lines could neither induce nor be killed by tumor-specific lymphocytes, suggesting that selection had been exerted against tumor cells expressing the tumor-specific antigen. No selection against natural killer [NK] cell activity or against nonspecific T cell-mediated immunity seems to have occurred because progressor tumor cells were highly sensitive to these types of effector cells and induced these effector cells more effectively than did the parental tumor. Nude mice were as capable as normal mice in generating NK activity in response to a challenge with progressor tumor cells but they were unable to mount a nonspecific T lymphocyte response. This may account for the fact that the progressor tumors grew at a significantly faster rate in nude animals than in normal mice. Thus, in this tumor system, nonspecific T cell-mediated immunity may play a role in retarding tumor growth but the absolute resistance of normal animals to progressive tumor growth critically depends upon the presence of T cell-mediated tumor-specific immunity. Neither NK cells nor nonspecific cytotoxic T lymphocytes appear to play a role in immunoselection against this tumor in normal immunocompetent hosts.