Lysis of syngeneic solid tumor cells by alloantigen stimulated mouse T and non-T cells.

Abstract

Abstract Based on previous studies suggesting that many tumor cells express cell surface antigens shared or cross-reactive with alloantigens, experiments were performed to determine whether in vitro stimulation of mouse spleen cells with allogeneic normal cells would result in cytotoxicity against syngeneic solid tumor cells. C56BL/6 or BALB/c spleen cells stimulated for 5 days with allogeneic normal cells caused significant lysis of syngeneic melanoma and fibrosarcoma cells but not syngeneic PHA blasts. Although lysis of allogeneic target cells and syngeneic leukemia cells by the allo-sensitized spleen cells was mediated by effector cells that are sensitive to treatment with anti-θ serum and C, lysis of syngeneic solid tumor cells was mediated by effector cells that were partially or totally resistant to anti-θ treatment. Further evidence that allo-stimulation can result in non-T cell-mediated lysis of syngeneic solid tumor cells derives from findings that i) preirradiation (1000 R) of responding spleen cell donors does not prevent the development of anti-tumor cytotoxicity although it ablates both proliferative and cytotoxic T cell responses; ii) anti-θ resistant effector cells cytotoxic for syngeneic tumors are detected within 16 hr after allo-stimulation when cytotoxic T lymphocyte (Tc) activity is not detectable; and iii) spleen cells from BALB/c homozygous nude mice generated low levels of cytotoxicity against syngeneic tumor cells but not allogeneic target cells after allo-stimulation. These results, together with findings that the solid tumor cells used for these studies were susceptible to lysis by poly I:C-activated natural killer (NK) cells, suggest that allo-stimulation not only leads to the generation of Tc but also to the activation of NK cells cytotoxic for syngeneic solid tumor cells.