title: In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity.
abstract: It remains unclear how the immune system affects leukemia development. To clarify the significance of the presence of immune systems in leukemia development, we transferred MLL/ENL leukemia cells into immune-competent or immune-deficient mice without any preconditioning including irradiation. The wild-type mice did not develop leukemia, whereas all the Rag2(-/-)γc(-/-) mice lacking both adaptive immune cells and natural killer (NK) cells developed leukemia, indicating that leukemia cells were immunologically rejected. Interestingly, leukemia cells were also rejected in 60% of the Rag2(-/-) mice that lacked adaptive immune cells but possessed NK cells, suggesting that NK cells play a substantial role in the rejection of leukemia. Moreover, engraftment of leukemia cells was enhanced by NK cell depletion in Rag2(-/-) recipients and inhibited by transfer of NK cells into Rag2(-/-)γc(-/-) recipients. Upregulation of NKG2D (NK group 2, member D) ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK cells. Finally, we found that leukemia cells resistant to elimination by NK cells had been selected during leukemia development in Rag2(-/-) recipients. These results demonstrate that NK cells can eradicate MLL/ENL leukemia cells in vivo in the absence of adaptive immunity, thus suggesting that NK cells can play a potent role in immunosurveillance against leukemia.
authors: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: J
authors: J
authors: Nakata
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: K
authors: K
authors: Nakano
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: A
authors: A
authors: Okumura
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Y
authors: Y
authors: Mizutani
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: H
authors: H
authors: Kinoshita
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: M
authors: M
authors: Iwai
authors: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: K
authors: K
authors: Hasegawa
authors: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: S
authors: S
authors: Morimoto
authors: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: F
authors: F
authors: Fujiki
authors: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: N
authors: N
authors: Tatsumi
authors: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: H
authors: H
authors: Nakajima
authors: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Y
authors: Y
authors: Nakae
authors: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: S
authors: S
authors: Nishida
authors: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: A
authors: A
authors: Tsuboi
authors: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Y
authors: Y
authors: Oji
authors: 1] Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan [2] Department of Immunopathology, WP1 Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors: Y
authors: Y
authors: Oka
authors: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: H
authors: H
authors: Sugiyama
authors: 1] Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan [2] Department of Immunopathology, WP1 Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors: A
authors: A
authors: Kumanogoh
authors: 1] Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan [2] Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: N
authors: N
authors: Hosen
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C527086:Klrk1 protein, mouse; C425207:MLL-ENL oncoprotein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D051788:Myeloid-Lymphoid Leukemia Protein