title: Glycosylation Status of CD43 Protein Is Associated with Resistance of Leukemia Cells to CTL-Mediated Cytolysis.
abstract: To improve cancer immunotherapy, it is important to understand how tumor cells counteract immune-surveillance. In this study, we sought to identify cell-surface molecules associated with resistance of leukemia cells to cytotoxic T cell (CTL)-mediated cytolysis. To this end, we first established thousands of monoclonal antibodies (mAbs) that react with MLL/AF9 mouse leukemia cells. Only two of these mAbs, designated R54 and B2, bound preferentially to leukemia cells resistant to cytolysis by a tumor cell antigen-specific CTLs. The antigens recognized by these mAbs were identified by expression cloning as the same protein, CD43, although their binding patterns to subsets of hematopoietic cells differed significantly from each other and from a pre-existing pan-CD43 mAb, S11. The epitopes of R54 and B2, but not S11, were sialidase-sensitive and expressed at various levels on leukemia cells, suggesting that binding of R54 or B2 is associated with the glycosylation status of CD43. R54high leukemia cells, which are likely to express sialic acid-rich CD43, were highly resistant to CTL-mediated cytolysis. In addition, loss of CD43 in leukemia cells or neuraminidase treatment of leukemia cells sensitized leukemia cells to CTL-mediated cell lysis. These results suggest that sialic acid-rich CD43, which harbors multiple sialic acid residues that impart a net negative surface charge, protects leukemia cells from CTL-mediated cell lysis. Furthermore, R54high or B2high leukemia cells preferentially survived in vivo in the presence of adaptive immunity. Taken together, these results suggest that the glycosylation status of CD43 on leukemia is associated with sensitivity to CTL-mediated cytolysis in vitro and in vivo. Thus, regulation of CD43 glycosylation is a potential strategy for enhancing CTL-mediated immunotherapy.
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 Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nakano
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okumura
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fujioka
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Urakawa
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 Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.affiliation: Department of Fundamental Biosciences, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Hirata
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; D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D019008:Drug Resistance, Neoplasm; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006031:Glycosylation; D006801:Humans; D007167:Immunotherapy; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism*; D051917:Leukosialin / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
chemical_list: D000939:Epitopes; D051917:Leukosialin; C465014:SPN protein, human; C497863:Spn protein, mouse; D019158:N-Acetylneuraminic Acid