In vivo activity of lymphokine-activated macrophages in host defense against neoplasia

Purified splenic macrophage (Mφ) from normal DBA/2J mice and mice bearing P815 tumors were examined for responsiveness to lymphokine (LK) preparations containing high concentrations of IFN-γ. For both normal and tumor-bearing Mφ, LK treatment induced morphologic changes and increased the percentage of Ia⁺ cells from 35 to 55%. Although neither population exhibited spontaneous cytotoxicity toward P815 targets, LK treatment induced considerable tumoricidal activity in tumor-bearing Mφ (32 to 80% lysis) but only minimal activity in normal Mφ (8 to 17% lysis). Subcutaneous injection of 1 x 10⁶ P815 cells into DBA/2J led to progressive tumor growth and death of 100% of the recipients after 27 ± 3 days. Injection of a 1:18 mixture of P815 with either LK-activated normal or tumor-bearing Mφ caused tumor regression after 10 days, and prolonged life until 43 ± 4 days with tumor-bearing Mφ and 39 ± 3 days with normal Mφ. Untreated normal or tumor-bearing Mφ were unable to cause the effect (30 ± 2 days), and lymphocytes could not be substituted for Mφ (25 ± 3 days). In x-irradiated recipients, no effect of LK-activated Mφ could be observed (control = 19 ± 2 days; LK-activated tumor-bearing Mφ = 21 ± 3 days). In addition, administration of an admixture of LK-treated Mφ and x-rayed tumor before challenge with viable P815 enabled the recipient to inhibit tumor growth and caused tumor necrosis with inflammatory cell infiltration of the tumor. These observations suggest that, in part, LK-activated Mφ may interact in vivo with host-derived cellular components and enhance the immune reactivity of the host against the tumor.