title: IFN-γ promotes graft-versus-leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic cell transplantation.
abstract: The ability of IFN-γ to enhance graft-versus-leukemia (GVL) activity without direct interaction with leukemia cells was examined by comparing GVL effects against IFN-γ receptor-deficient (GRKO) leukemia between wild-type (WT) and IFN-γ-deficient (GKO) allogeneic hematopoietic cell transplantation (allo-HCT). We established a primary IFN-γ-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 pre-established 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-γ is capable of promoting GVL effects via mechanisms independent of its interaction with leukemia cells.
authors.affiliation: First Bethune Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Beow Yong
authors.initials: BY
authors.lastname: Yeap
authors.forename: Tingting
authors.initials: T
authors.lastname: Liang
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D020544:Graft vs Leukemia Effect / Q000187:drug effects* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous; D015854:Up-Regulation / Q000187:drug effects; D000096743:Interferon gamma Receptor
chemical_list: D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor