Host reactivity to a spontaneous tumor: generation of antitumor activity by lymph node cells following incubation in vitro.

A spontaneous fibrosarcoma (SP/T-1) which arose in a syngeneic Balb/c mouse failed to show clear evidence of immunogenicity when examined by the in vivo immunization/challenge technique. However, when the lymph node cells (LNC) of tumor-'immunized' donors were cultured in vitro for approximately 2 days in the absence of tumor cells, they were found to be markedly inhibitory to the tumor in cell transfer assays. A similar effect was also found in the LNC of tumor-bearers but this was less marked. The antitumor activity appeared to be mediated largely by the T cells, since the depletion of Thy 1 positive cells abolished or markedly decreased the LNC inhibitory activity towards the tumor cells. The activated LNC were found to be specifically cytotoxic to the SP/T-1 cells since they did not destroy cells of two other syngeneic cell types tested--a methylcholanthrene-induced fibrosarcoma, MC677 and a neonatal heart-derived normal cell line NEO/H. Neither of these cell types showed virus particles by electron microscopy and since C type virus-like particles were detected within the SP/T-1 cells by electron microscopy the possibility exists that viral antigenic determinants expressed on the tumor cell surface acted in tumor cell recognition and destruction in this tumor system. However, the possibility cannot be excluded that in vitro-activated natural killer cells also participated in tumor cell killing. These observations clearly indicate the existence of tumor-associated transplantation antigens in certain 'non-immunogenic' tumors as well as antitumor effector mechanisms which remain totally suppressed in vivo.