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Modulation of the Cytotoxic Response against Allogeneic Tumor Cells in Culture by Adriamycin¹

Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263

Adriamycin exerts selective effects on the primary allogeneic immune response in culture, depending on dose, schedule of administration, and culture conditions. Inhibition of the response was seen if the drug had been present for 24 hr during the first 36 hr of culture. Even at the same concentrations at which suppressive effects were observed but under slightly different conditions of sensitization, there was an increase in the immune cytotoxic response. The augmenting effect was observed especially under conditions where the control lytic response was low.

Addition of Adriamycin to the culture 24 hr before, at the same time as, or as late as 48 hr after antigen augmented the development of the cytotoxic response in comparison to untreated controls. Treatment of spleen cells in culture with silica 24 hr before antigenic stimulation abrogated the development of the cytotoxic response to allogeneic tumor cells. Following simultaneous addition of Adriamycin and silica 24 hr before antigenic stimulation, the response was only somewhat lower than the response of untreated spleen cells. Similar results were obtained following addition of silica 24 hr before the addition of Adriamycin and antigenic stimulation. These findings suggest that Adriamycin affects a silica-insensitive population of cells. Spleen cells which had been treated with Adriamycin for 24 hr in culture were separated by adherence to plastic. The two populations were recombined with nontreated separated cells and stimulated with antigen. The ability to develop an augmented response was associated with the nonadherent fraction of Adriamycin-treated spleen cells. When the Adriamycin-treated spleen cells were separated after 4 days of antigenic stimulation, an augmented cytotoxic response was observed in both fractions. All adherent and nonadherent effector cells were positive.

In conclusion, the augmented response observed in culture after addition of Adriamycin seems related to effects on a silica-resistant nonadherent fraction of spleen cells, leading to the development of a greater response by T-effector cells.

¹ This work was supported in part by USPHS Contract CM-57039 and Core Grant CA-24538-01 from the National Cancer Institute.

Received 7/19/79. Accepted 5/ 1/80.