title: An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells.
abstract: Leukemia differs substantially with respect to stromal milieu from tumors that progress locally as solid masses, and the physiological importance of immunosurveillance in leukemia remains unclear. However, currently available mouse leukemia models have critical limitations in the context of analyzing immunological regulation of leukemia development. In this study, we transferred mouse MLL/AF9 leukemia-initiating cells into immunocompetent recipient mice without any pre-conditioning such as irradiation, and then analyzed the spontaneous T cell response to an immunogenic antigen expressed in leukemia cells. When the minimum numbers of leukemia-initiating cells for engraftment were transferred, leukemia cells were eradicated by the adaptive immune response in most, if not all, wild-type mice, but not in Rag2-/- recipient mice, which lack adaptive immunity. By contrast, mice transplanted with larger numbers of leukemia cells always developed leukemia. In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3. These results provide the first clear demonstration that the spontaneous CTL response to a tumor-cell antigen has the potential to eradicate leukemia, whereas antigen-specific CTLs are exhausted in animals with advanced leukemia. This immunocompetent mouse leukemia model provides a useful platform for developing effective immunotherapies against leukemia.
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujiki
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Soyoko
authors.initials: S
authors.lastname: Morimoto
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Tatsumi
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakata
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Immunopathology, WP1 Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Immunopathology, WP1 Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007121:Immunocompetence; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D051788:Myeloid-Lymphoid Leukemia Protein