Delayed-hypersensitivity reactions to soluble membrane antigens of human malignant lung cells.

Abstract

Membrane preparations of human lung cancer cells, of “normal” lung cells from the same patient, and of normal lung cells from a healthy accident victim did not produce delayed-hypersensitivity reactions when 0.1 ml amounts, containing a range of 17–1232 μg membrane protein, were used in 48 intradermal skin tests of lung cancer patients. When these same membrane preparations were subjected to sequential, low-frequency sonication and the soluble portions of the membranes were partially separated on Sephadex G-200 into high- and lowmolecular weight protein fractions, 50 of 106 tests with fractions of lung cancer sonicates and 19 of 106 of “normal” lung-sonicate fractions from the cancer patients produced positive delayed-hypersensitivity skin reactions in autologous and allogeneic lung cancer patients. A patient with epidermoid lung cancer was also tested with fractions from normal lung cell-membrane sonicates obtained from the healthy accident victim; the high-molecular weight fraction produced a borderline positive response. Allogeneic tests on a patient with epidermoid lung cancer were performed with the soluble antigens, both from epidermoid cancer cells and from metastatic tumors growing in the lungs of patients with intestinal and cervical cancers; only the epidermoid lung cancer-soluble antigens gave positive tests. The soluble antigens were further separated by special gradient gel electrophoresis and elution of sliced regions of the gels. A total of 99 skin tests on 9 patients with oat cell carcinoma, epidermoid carcinoma, and adenocarcinoma were performed with the soluble antigens obtained from these gel regions prepared from 5 tumors, 5 adjacent lung preparations, and healthy lung. Positive skin reactions to antigens from adjacent lung and healthy lung preparations were mainly from regions I and II. Positive skin reactions to antigens from epidermoid carcinomas were mainly from regions I, II, and III. The strongest positive delayed-hypersensitivity skin reactions were to oat cell carcinoma and adenocarcinoma antigens from regions III and IV. Reactions were negative in a nonanergic patient with lymphosarcoma arising in the bronchus and in a nonanergic patient with breast cancer when tested with antigens from all gel regions of a healthy lung preparation. A total of 9 patients with malignant, nonpulmonary disease were skin-tested with all gel regions from a preparation of epidermoid lung cancer; all skin tests were negative. Thus skin tests in which separated lung cancer-soluble antigens are used produce delayed-hypersensitivity responses in lung cancer patients. We concluded that this reactivity was directed to certain antigens also present in some normal lung preparations as well as to certain antigens in lung cancer preparations which appeared to differ from the normal antigens, thus suggesting some tumor specificit.