Splenic natural cytotoxic activity is enhanced during growth of a murine fibrosarcoma.

We have shown previously that the natural killer (NK) cell activity of DBA/2J mice bearing M-1 fibrosarcomas is consistently depressed at the later stages of tumor growth. The apparent mechanisms of inhibition are suppressor cell activation and prostaglandin E (PGE) production by tumor and lymphoid cells. In contrast, we show here that the natural cytotoxic (NC) activity of cells from the spleen, blood, and lymph nodes of mice bearing M-1 tumors is enhanced when compared to that of age- and sex-matched control mice. This enhanced NC activity does not appear to be due to increased cytolytic activity of macrophages but, rather, to enhanced cytolytic activity of multiple populations of non-adherent cells including B and T cells. Correlated with this is the finding that the NC activity of normal spleen cells is not inhibited in vitro by either PGE1 or PGE2 at levels which are inhibitory to NK cells. NC activity, although independent of PGE, is in fact enhanced by PGE1 in a dose-related fashion. These data indicate that NK and NC cells are regulated differently by PGE and during tumor growth. Utilizing a Winn assay, we also demonstrate that a cloned cell line with NC activity is capable of slowing tumor growth in vivo and that this action is improved if mice are treated with indomethacin concomitantly.