Branched I antigens on leukemia cells enhanced sensitivity against natural killer–cell cytotoxicity through affecting the target–effector interaction

Yen Hua Lee, Yi Jen Liao, Chin Han Huang, Fu Ling Chang, Ting Hsi Fan, Yuh Ching Twu

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector–target interactions by cytotoxic analysis and conjugate formation assay. RESULTS: We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I– cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis. CONCLUSION: In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector–target interaction.
原文英語
頁(從 - 到)1040-1051
頁數12
期刊Transfusion
57
發行號4
DOIs
出版狀態已發佈 - 四月 1 2017

指紋

Leukemia
Natural Killer Cells
Tumor-Associated Carbohydrate Antigens
Neoplasm Metastasis
Ligands
Immunologic Monitoring
Blood Group Antigens
Glycosylation
Cell Communication
Immunity
Flow Cytometry
Carcinogenesis
Clinical Trials
Lipids
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

引用此文

Branched I antigens on leukemia cells enhanced sensitivity against natural killer–cell cytotoxicity through affecting the target–effector interaction. / Lee, Yen Hua; Liao, Yi Jen; Huang, Chin Han; Chang, Fu Ling; Fan, Ting Hsi; Twu, Yuh Ching.

於: Transfusion, 卷 57, 編號 4, 01.04.2017, p. 1040-1051.

研究成果: 雜誌貢獻文章

Lee, Yen Hua ; Liao, Yi Jen ; Huang, Chin Han ; Chang, Fu Ling ; Fan, Ting Hsi ; Twu, Yuh Ching. / Branched I antigens on leukemia cells enhanced sensitivity against natural killer–cell cytotoxicity through affecting the target–effector interaction. 於: Transfusion. 2017 ; 卷 57, 編號 4. 頁 1040-1051.
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abstract = "BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector–target interactions by cytotoxic analysis and conjugate formation assay. RESULTS: We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I– cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis. CONCLUSION: In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector–target interaction.",
author = "Lee, {Yen Hua} and Liao, {Yi Jen} and Huang, {Chin Han} and Chang, {Fu Ling} and Fan, {Ting Hsi} and Twu, {Yuh Ching}",
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T1 - Branched I antigens on leukemia cells enhanced sensitivity against natural killer–cell cytotoxicity through affecting the target–effector interaction

AU - Lee, Yen Hua

AU - Liao, Yi Jen

AU - Huang, Chin Han

AU - Chang, Fu Ling

AU - Fan, Ting Hsi

AU - Twu, Yuh Ching

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N2 - BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector–target interactions by cytotoxic analysis and conjugate formation assay. RESULTS: We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I– cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis. CONCLUSION: In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector–target interaction.

AB - BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector–target interactions by cytotoxic analysis and conjugate formation assay. RESULTS: We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I– cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis. CONCLUSION: In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector–target interaction.

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