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

Abstract

AbstractIn an attempt to analyze mechanisms of immunity against tumor metastases, protective anti‐tumor immunity in vivo was compared with cytotoxic T‐cell activity in vitro in a well‐defined syngeneic tumor model system. The system consists of a chemically induced parental tumor 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 (TATAs) on both Eb and ESb tumor cells. TATAs of Eb and ESb were found to be distinct and non‐cross‐reactive. One of several unrelated tumors, however, RL♂1, expressed TATAs which cross‐reacted with those of Eb. Protective immunity against the non‐metastasizing tumor was much stronger than that against the metastasizing variant. Furthermore, the optimal procedures for induction of immunity in vivo were strikingly different for each tumor. Tumor‐specific cytotoxic T lymphocytes (CTLs) 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. Both anti‐Eb and anti‐ESb CTLs showed high cytolytic activity in a 4‐h 51Cr release assay against the autologous tumor lines. The target antigens recognized by these cells were similar to the TATAs as defined in the protection experiments. (1) The target antigens of Eb and ESb were distinct and non‐cross‐reactive. (2) Only one of 14 unrelated syngeneic and allogeneic tumors expressed a target antigen which cross‐reacted with that of Eb. (3) This tumor was the radiation‐induced BALB/c lymphoma RL♂1 which also cross‐reacted at the level of the TATAs. The correlations between protective immunity obtained in vivo and cytolytic T cells induced in vitro suggest that cytolytic T cells can recognize TATAs and may thus play an important role in the establishment of protective immunity.