Sensitivity of cloned high- and low-metastatic murine Lewis lung tumor cells to lysis by cytotoxic autoreactive cells.

Cloned malignant cell lines from primary tumor sites (two lines) and from a lung metastatic focus (one line) were established 14 and 28 days after s.c. inoculation of Lewis lung tumor cells into C57BL/6 mice. Cloning was done in semisolid agarose culture medium and individual clones expanded in liquid medium. In vivo malignancy of the three lines was assured by graft experiments to healthy C57BL/6 recipients. Morphology, cloning efficiency in agarose, and growth rate were the same for all three lines. However, the cloned line from a metastatic focus had a higher metastatic rate (number of lung metastases per 10(5) injected tumor cells) compared to the two other cell lines. T-lymphocyte-depleted mononuclear spleen cells from mice grafted with tumor cells 2 to 4 weeks previously were found to be cytotoxic to cells from all three lines, whereas unfractionated mononuclear spleen cells from the same animals had weak or no cytotoxic activity. The cytotoxicity of T-lymphocyte-depleted spleen cells was found to include other malignant and nonmalignant target cells of C57BL/6 origin, but not allogeneic cells. In mixing experiments, splenic T-lymphocytes inhibited the cytotoxic activity of non-T-lymphocytes. The high- and low-metastatic tumor cell lines were found to be equally sensitive to lysis by T-cell-depleted spleen cells, suggesting that the effector cells (cytotoxic autoreactive cells) may have a significant antineoplastic potential.