Inhibition of normal allogenic lymphocyte mitogenesis by a soluble inhibitor extracted from human colonic carcinoma

Soluble extracts from human colonic tumors (STE) and from their hepatic metastases (SHME) were found to be unable to induce a proliferative response among normal allogenic lymphocytes. However, addition of these tissue extracts to cultures stimulated with various mitogens resulted in an almost complete inhibition of lymphocyte DNA synthesis. Nevertheless, they did not reduce the unstimulated lymphocyte spontaneous proliferation. Control experiments have shown that normal or nonmalignant tissues do not affect the lymphocyte reactivity to mitogens. The specific immunosuppressive evvect was found to be irreversible and to block lymphocyte activation at an early stage. The inhibitor was soluble (not sedimented at 220,000 times G for 2 hr) and not nonspecifically cytotoxic. STE was slso found to induce morphologic alterations resulting in blastlike cell production. However, no mitotic figures were seen, even after colchicin treatment. It is suggested that STE might contain molecular component(s) which would exert a double effect: 1) trigger metabolic alterations responsible for the blast-like cell induction, and 2) inhibit the lymphoproliferative response. The significance of such a mechanism is discussed in conection with the nonspecific immunosuppression caused by a tumor and the immune unresponsiveness against the tumor itself. A preliminiary characterization of this tumor material has shown that its molecular weight was about 70,000 and that it is not related to carcinoembryonic antigen or alpha-fetoprotein.