Tumor-specific immune responsiveness of the tumor-bearing host

In vitro lymphocyte stimulation by mitomycin-C-blocked tumor cells has been used to demonstrate tumor-specific antigens in methylcholanthrene-induced sarcomas and in syngeneic murine systems, and to follow the evolution of tumor immunity in the tumor-bearing state. Lymphocytes from normal mice, from mice bearing small methylcholanthrene-induced tumors (less than 1 cm in diameter) and from tumor-immunized mice (which had been sensitized by tumor cell inoculation and subsequent tumor (removal) were stimulated by mitomycin-C-blocked tumor cells to undergo increased DNA synthesis in culture. However, lymph node cells from mice with large methylcholanthrene-induced tumors (greater than 1 cm in diameter) had quite different characteristics. The background DNA-synthetic activity of lymph node cells from tumor-bearing mice was much higher than that of lymph node cells from normal mice or from preimmunized, non-tumor-bearing mice, and progressively increased with the duration of tumor-bearing and the size of the tumor. Lymph node cells from mice bearing large tumours appeared to be maximally stimulated by the tumor in vivo and were incapable of further stimulation by the same tumor cells in vitro, but exhibited normal responses to other antigens and nonspecific mitogens. Lymph node cells from mice bearing large tumors depleted of the adherent cells had lower background levels of DNA synthetic activity per 10(6) cells and underwent stimulation similarly to lymphoid cells from preimmunized, non-tumor-bearing mice. Spleen cells from mice bearing large tumors also had increased background levels of DNA synthetic activity, but contrary to the observations made with the lymph node cells, they were able to undergo further stimulation when cultured with the same tumor cells. Studies on the background incorporation of tritiated thymidine by lymph node cells from tumor-bearing mice revealed that the spontaneous uptake of reconstituted populations was nearly that of the original population and more than twice that of the arithmetical sum of the nonadherent and the adherent subpopulations. This was not found with normal lymph node cells or with spleen cells from normal or tumor-bearing mice. The differential effects observed with lymph node cells compared to spleen cells from tumor-bearing mice are emphasized and possible explanations for these findings are discussed.