Inhibition of tumor growth in immunocompromised hosts by restoring type-2 immunity using infusion of G-CSF-treated allogeneic CD8+ leukocytes.

Since recombinant human granulocyte colony-stimulating factor (rhG-CSF)-treated donor leukocyte infusion (G-DLI) has been shown to downregulate type-1 immunity in a heart transplant model, we examined influences of G-DLI on tumor growth in immunosuppressed hosts. F344 rats were treated with tacrolimus (8 mg/kg i.m.) and syngeneic colon adenocarcinoma RCN-9 cells (3 x 10(6)) were inoculated subcutaneously. For G-DLI, allogeneic DA rats were pretreated with rhG-CSF (250 microg/kg, days -5 to 0) and isolated leukocytes or sorted CD8(+) cells were injected intravenously to the hosts on day 0. Tumors in tacrolimus-treated hosts continuously grew over 5 weeks. G-DLI of 100 x 10(6) leukocytes attenuated tumor growth rate while direct host pretreatment with rhG-CSF did not. Notably, G-DLI of 10 x 10(6) CD8(+) cells blocked tumor expansion after day 14. Tacrolimus-induced inhibition of lymphocyte infiltration into tumors was recovered by the G-DLIs. Flow cytometry showed no detectable donor-type T cells in the tumor and circulation. Quantification of intratumor transcription levels using reverse transcription-real-time polymerase chain reaction showed recovery from tacrolimus-induced downregulation of interleukin-4 but not interferon-gamma levels. In vivo rhG-CSF-treated CD8(+) allogeneic cells demonstrate potent anti-tumor effects by restoring type-2 immunity of immunosuppressed hosts.