Escape of TA3 tumors from allogeneic immune rejection: theory and experiments

Abstract

Abstract A factor promoting tumor growth in allogeneic mice was found in the ascites fluid of TA3‐Ha tumor‐bearing mice. Preliminary attempts to isolate this factor resulted in a preparation (P3), devoid of free immunoglobulins or serum proteins, which had enhanced action in promoting tumor growth in vivo . Electron microscopy showed that the P3 preparation is of membranous origin. Biochemical assays for membrane marker enzymes were positive. 5′ ‐Nucleotidase and alkaline α‐glycerophosphatase activity was found. Chemical and gas‐liquid chromatographic analysis of long‐chain carboxylic acids present in the tumor cell membrane and in the P3 revealed the presence of fatty acids in almost identical ratios in both preparations, again indicating the membranous character of P3. The P3 preparation as well as the ascites fluid have immunogenic properties. They could induce immune tolerance if injected neonatally and the P3 preparation could immunize against the TA3‐Ha tumor if injected intramuscularly or subcutaneously into adult mice. It had no effect if injected intravenously. In vitro studies of the mode of action of the tumor growth facilitating component indicate that it acts through reaction with immunocytes. A cytotoxic effect of ascites fluid on normal thymocytes in the presence of added complement could be demonstrated. Exposure of immune spleen cells to ascites fluid abrogated their ability to adoptively transfer resistance. A working hypothesis has been proposed according to which TA3‐Ha tumor cells produce highly reactive membranous decay products which intercept incoming immunocytes or immunoglobulins before they can reach their targets on living tumor cells. Whether this self protection of TA3 ascites tumors can be applied to other tumors remains to be investigated.