Depression of alloantigens in malignancy. Evidence for tumour susceptibility alloantigens and for possible self-reactivity of lymphoid cells active in the microcytotoxicity assay.

Inbred strains of mice were found to differ markedly in both susceptibility to the spontaneous development of malignant alveologenic lung tumours and the ease with which these tumours could be induced with chemical carcinogens administered to adult animals. Malignant lung tumours occurred in normal strain A mice but were very rare in normal C3Hf, DBA/2 and C57BL/6 mice or in these mice treated as adults with the carcinogen 1-ethyl-1-nitrosourea (ENU). Malignant tumours could, however, be induced in C3Hf mice exposed prenatally to ENU. Two transplacentally induced malignant lung tumours of C3Hf mice failed to grow when transplanted to normal C3Hf recipients but did grow progressively when transplanted into either (C3Hf × A) F hybrid or C3H recipients. The tumours grew progressively in sublethally x-irradiated but otherwise untreated C3Hf mice. Immunization of C3Hf mice with either of the lung tumours, or with normal lung tissue of either A or C3H mice, induced a degree of radioresistant immunity such that tumour cells inoculated into immunized, sublethally x-irradiated mice, failed to grow progressively. Radioresistant immunity was not induced when C3Hf mice were immunized with lung tissue of DBA/2 or C57BL/6 mice. Lymphoid cells of (C3Hf × A) F and C3H mice bearing transplanted C3Hf lung tumour reacted against cultured lung tumour cells in the microcytotoxicity assay. Reactivity was also observed against cells cultured from normal lungs of C3H and (C3Hf × A) F mice but not against cells cultured from normal lungs of C3Hf or C57BL/6 mice. These results were interpreted to indicate that transplacentally induced malignant lung tumours of C3Hf mice express an antigenic component which exists as a normal tissue alloantigen, present in A and C3H but not in C3Hf, DBA/2 or C57BL/6 mice. It was suggested that the normal expression of the alloantigen in A mice may contribute to the susceptibility of these mice to the spontaneous development of lung tumours. The observation that a tumour bearing host has lymphoid cells reactive in the microcytotoxicity assay against tumour cells does not necessarily indicate that the tumour possesses a tumour specific antigen for in genetically susceptible tumour bearing hosts, the reaction may be directed against a self-antigen.