Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. VI. Similar specificity patterns of protective anti-tumor immunity in vivo and of cytolytic T cells in vitro
Bosslet, K.; Schirrmacher, V.; Shantz, G.
International Journal of Cancer 24(3): 303-313
ISSN/ISBN: 0020-7136 PMID: 314938 DOI: 10.1002/ijc.2910240306
In an attempt to analyze mechanisms of immunity against tumor metastases, protective anti-tumor immunity in vivo was compared with cytotoxic T[thymus-derived]-cell activity in vitro in a well-defined syngeneic tumor model system. The system consisted of a chemically induced parental tumor [lymphoma] cell line (Eb) with little or no metastatic potential and a spontaneous variant thereof (ESb) with pronounced metastatic properties. Tumor protection experiments revealed the presence of tumor-associated transplantation antigens (TATA) on Eb and ESb tumor cells. TATA of Eb and ESb were distinct and non-cross-reactive. One of several unrelated tumors, Rl.male.1, expressed TATA which cross-reacted with those of Eb. Protective immunity against the non-metastasizing tumor was much stronger than that against the metastasizing variant. Optimal procedures for induction of immunity in vivo were strikingly different for each tumor. Tumor-specific cytotoxic T lymphocytes (CTL) were obtained after sensitization in vivo with viable tumor cells and restimulation in vitro for 4-5 days with mitomycin-C-treated autologous tumor cells. Anti-Eb and anti-ESb CTL showed high cytolytic activity in a 4-h 51Cr release assay against the autologous tumor lines. Target antigens recognized by these cells were similar to the TATA as defined in the protection experiments. The target antigens of Eb and ESb were distinct and non-cross-reactive. Only 1 of 14 unrelated syngeneic and allogeneic tumors expressed a target antigen which cross-reacted with that of Eb. This tumor was the radiation-induced BALB/c lymphoma RL.male.1 which also cross-reacted at the level of the TATA. Correlations between protective immunity obtained in vivo and cytolytic T cells induced in vitro suggest that cytolytic T cells can recognize TATA and may thus play an important role in establishment of protective immunity.