SPECIFICITY OF CONCOMITANT TUMOR IMMUNITY AT LARGE TUMOR VOLUMES

  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (10) , 3690-3694
Abstract
Two antigenically distinct fibrosarcomas, designated BP-8 and BP-9, induced in syngeneic C3H/HeN mice by 3,4-benzo(a)pyrene were used to study tumor specific immunity, concomitant tumor immunity and the effect of large tumor volumes on the loss of immunological reactivity. Two groups of mice were immunized to the BP-8 tumor by amputation of growing BP-8 isografts. One group was rechallenged with BP-8 cells, and tumor growth was not noted. Both groups of mice then received an inoculum of BP-9 cells that grew to palpable tumors to the same extent as in control mice. BP-8-immunized mice bearing progressively larger BP-9 tumors were sacrificed at varying intervals after the BP-9 isograft. Tumor weight was recorded as a percentage of total body weight and viable spleen cells from these animals were tested in vitro for cytotoxicity against BP-8 and BP-9 cells in the [125I]iododeoxyuridine microcytotoxicity assay. Spleen cells from untreated mice were used as controls. Mice with growing BP-9 tumors developed an immune reaction against the tumor antigens which increased with time from initial tumor isograft and increasing tumor size up to a definite but variable limit. Cytotoxicity to BP-9 cells rose from 18% when the BP-9 tumor was not palpable to a maximum of 77% when the tumor represented 5-10% of the total body weight. Cytotoxicity to BP-9 fell progressively as tumor size exceeded 15% of the total body weight and approached the 10% background cytotoxicity of control lymphocytes to BP-9 cells when the tumor weight achieved 25% of the animal''s weight. Cytotoxicity of lymphocytes against the BP-8 tumor did not vary significantly and remained about 41-44% over the same interval even while specific reactivity to BP-9 cells significantly decreased. With time, lymphocyte mediated cytotoxicity to the BP-8 tumor increased from 41-70% if the BP-8-immunized mice were rechallenged with antigenically identical BP-8 cells prior to the BP-9 isograft. These data suggest that loss of immunoreactivity at large tumor volumes is tumor and, presumably, antigen specific. No evidence of a generalized immune paralysis was demonstrated, since the mice always maintained immunity to the BP-8 tumor despite progressive and lethal growth of the antigenically distinct BP-9 tumor.

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