Depression of antilymphoma allograft reactivity by tumor-associated factors.

Abstract

Relatively small numbers of viable or killed tumor cells (102 to 105) of five transplantable mouse leukemias and one carcinoma were inoculated into syngeneic or allogeneic adult mice. The inoculations depressed the allograft reactivity of the recipients as judged from reduced resistance to the growth of a second transplant of 106 to 107 H-2 -incompatible strain-specific lymphoma cells. A single injection of the most effective conditioning cells caused long-lasting depression of antilymphoma reactions (up to 3 months) regardless of whether the H-2 antigens of challenging and conditioning tumors were different or alike. The active factor was extractable from cells in suspension and separable by filtration through Millipore membranes. Of 338 mice pretreated with tumor material under a variety of conditions and schedules, 326 were rendered susceptible to allogeneic lymphoma grafts, whereas only 19 of 219 untreated control mice failed to reject the tumors. Depression of antilymphoma reactions was not caused by cells of normal spleen and of two other leukemias and one carcinoma. However, lactic dehydrogenase-elevating virus, a contaminant of all tumors used, and Moloney sarcoma virus did cause nonspecific depression, thus imitating the tumors. Depressive factors capable of breaking the major histocompatibility barrier of the species (possibly viruses, viral products, or tumor cell products) were associated with as few as 100 neoplastic cells. If this association would also occur during oncogenesis, it could favor the escape of antigenic tumors from host surveillance.