SUBVERSIVE ACTIVITY OF SYNGENEIC TUMOR CELLS AS AN ESCAPE MECHANISM FROM IMMUNE SURVEILLANCE AND THE ROLE OF PROSTAGLANDINS*

Abstract

Mice bearing a syngeneic tumor become increasingly immunodepressed during growth of the tumor, being unable to develop both cellular and humoral immunity to a histoincompatible tumor allograft and to reject the allograft. This failure to reject a strongly antigenic tumor allograft suggests that immunodepression associated with growth of a weakly antigenic syngeneic tumor provides the syngeneic tumor with an escape mechanism. This immunodepression is also manifest by the suppression of the response of spleen cells to mitogen stimulation by syngeneic tumor cells, both in vivo and in vitro. T cells that are stimulated by PHA, a T-cell mitogen, are the primary targets, and their suppression is the result of the direct subversive activity of the tumor cells. Subversion of T cells by tumor cells seems to be mediated through the prostaglandin pathway, because the prostaglandin PGE2 is itself suppressive, and an antagonist of PGE2 and an inhibitor of prostaglandin synthetases both inhibit the subversive activity of tumor cells. Several tumor cell lines tested, of different etiology and histologic type, all were subversive. This suggests that this subversive activity may be a general property of tumor cells and may be a key element in their ability to thwart the immunological system of the host. For this reason, any therapeutic regimen of cancer, based on immunostimulating drugs, should include drugs that can inhibit active subversion of the immune system by the tumor itself. Antagonists of prostaglandins and inhibitors of prostaglandin synthetases show promise in this regard.