TUMORS WITH REDUCED EXPRESSION OF A CYTOTOXIC T-LYMPHOCYTE RECOGNIZEDANTIGEN LACK IMMUNOGENICITY BUT RETAIN SENSITIVITY TO LYSIS BY CYTOTOXIC T-LYMPHOCYTES

A murine solid tumor was transfected to express various levels of an a llogeneic major histocompatibility complex class I gene (K-216), in or der to test the effect of the level of antigen expression on immunogen icity and sensitivity to lysis by cytotoxic T lymphocytes (CTL). The g rowth rates of clones of tumor cells expressing different levels of th e transfected gene were similar in vitro and in nude mice. Although al l tumor cells, including cells freshly isolated from growing tumors;we re equally sensitive to lysis by specific CTL, only tumor cells expres sing the highest level of the K-216 antigen stimulated CTL and were re jected by normal mice. In contrast, tumor cells expressing lower level s of antigen failed to immunize for CTL and grew progressively in norm al mice, despite retaining expression of the transfected gene and rema ining fully sensitive to CTL-mediated lysis; thus, the threshold of an tigen needed to stimulate CTL responses was considerably higher than t hat needed to lyse tumor cells. Reduction of K-216 antigen expression from 100-fold to 40-fold above background, impaired significantly the ability of the tumor cells to induce a K-216-specific immune response, while tumor cells expressing K-216 at levels 2-fold above background were as susceptible to CTL-mediated lysis as tumor cells expressing 50 -fold more antigen. The important implication of these findings is tha t some tumors occurring in nature may not be immunogenic but neverthel ess express antigens which are potential targets for immune therapy.