The ability of IFN-gamma to enhance graft-versus-leukemia (GVL) activity without direct interaction with leukemia cells was examined by comparing GVL effects against IFN-gamma receptor-deficient (GRKO) leukemia between wild-type (WT) and IFN-gamma-deficient (GKO) allogeneic hematopoietic cell transplantation (allo-HCT). We established a primary IFN-gamma-unresponsive T-cell leukemia model using virally-transduced GRKO B6 mouse bone marrow cells overexpressing Notch1. We first assessed GVL effects in lethally-irradiated B6 mice receiving CD4-depleted allo-HCT from WT or GKO BALB/c donors. Administration of CD4(+) cell-depleted allo-HCT from WT, but not GKO, BALB/c donors mediated significant GVL effects against GRKO leukemia. Similar results were obtained in preestablished allogeneic chimeras receiving delayed donor lymphocyte infusion (DLI). Although both WT and GKO DLI achieved significant anti-tumor responses, the former was markedly stronger than the latter. These data indicate that IFN-gamma is capable of promoting GVL effects via mechanisms independent of its interaction with leukemia cells. (Blood. 2011; 118(13):3721-3724)
[1]Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA.
[2]Jilin Univ, Bethune Hosp 1, Changchun 130023, Jilin, Peoples R China.
[3]Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
[4]Univ Pittsburgh, Sch Med, Inst Canc, Canc Stem Cell Program,Dept Radiat Oncol, Pittsburgh, PA USA.
[5]Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[6]Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China.
[7]Chinese Acad Med Sci, Ctr Stem Cell Med, Tianjin, Peoples R China.
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