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; Twu, Yuh Ching

doi:10.1111/trf.13982

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…By non-radioactive cytotoxicity assay, the killing activities were significantly lower in the NK-92MI-S against three selected leukemia cell lines, at effector:target (E:T) ratios from 1:1 to 10:1, as opposed to those observed in parental NK-92MI ( Figure 1 A–C). On the other hand, consistent with our previous findings on the NK-92MI-resistant THP-1 cell line, there was no noticeable difference in cytotoxicity against this cell between two NK lines ( Figure 1 D) [ 41 ].…”

Section: Resultssupporting

confidence: 92%

“…Expression of cell surface glycans is known to be involved in many key regulatory functions during the immune response, like correlation with the cell transformation into the tumor and leukemia as well as the escape from host immunity, such as from cytotoxic T- and NK-mediated surveillance [ 41 , 53 ]. Currently, it is still not clear how expression of Siglec-7 is regulated in both therapeutic NK-92MI and normal human NK cells.…”

Section: Discussionmentioning

confidence: 99%

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A Developed NK-92MI Cell Line with Siglec-7neg Phenotype Exhibits High and Sustainable Cytotoxicity against Leukemia Cells

Huang

Liao

Fan

et al. 2018

IJMS

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Altered sialic acid processing that leads to upregulation of cell surface sialylation is recognized as a key change in malignant tissue glycosylation. This cancer-associated hypersialylation directly impacts the signaling interactions between tumor cells and their surrounding microenvironment, especially the interactions mediated by immune cell surface sialic acid-binding immunoglobulin-like lectins (Siglecs) to relay inhibitory signals for cytotoxicity. First, we obtained a Siglec-7neg NK-92MI cell line, NK-92MI-S7N, by separating a group of Siglec-7neg cell population from an eight-month-long-term NK-92MI in vitro culture by fluorescence-activated cell sorting (FACS). The effect of Siglec-7 loss on NK-92MI-S7N cells was characterized by the cell morphology, proliferation, and cytotoxic activity via FACS, MTS assay, cytotoxic assay, and natural killer (NK) degranulation assay. We found the expression levels of Siglec-7 in NK-92MI were negatively correlated with NK cytotoxicity against leukemia cells. This NK-92MI-S7N cell not only shared very similar phenotypes with its parental cells but also possessed a high and sustainable killing activity. Furthermore, this Siglec-7neg NK line was unexpectedly capable of eliminating a NK-92MI-resistant leukemia cell, THP-1, through enhancing the effector-target interaction. In this study, a NK cell line with high and sustainable cytotoxicity was established and this cell may provide a potential application in NK-based treatment for leukemia patients.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

A Developed NK-92MI Cell Line with Siglec-7neg Phenotype Exhibits High and Sustainable Cytotoxicity against Leukemia Cells

Huang

Liao

Fan

et al. 2018

IJMS

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“…GCNT2 has been widely studied in melanoma, the loss of which brings corresponding loss of I-antigen and thus enhances melanoma growth and metastasis [ 65 ]. Importantly, many studies have pointed out that the high level of I-antigen synthesized by GCNT2 could increase the susceptibility of malignant cells against immune cells in leukemia [ 66 , 67 ]. This kind of immune regulatory may account for why GCNT2 was upregulated in OC but a good prognostic predictor in our study.…”

Section: Discussionmentioning

confidence: 99%

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer

Jia

et al. 2023

J Ovarian Res

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Background Ovarian cancer (OC) is the most fatal gynaecological malignancy and has a poor prognosis. Glycosylation, the biosynthetic process that depends on specific glycosyltransferases (GTs), has recently attracted increasing importance due to the vital role it plays in cancer. In this study, we aimed to determine whether OC patients could be stratified by glycosyltransferase gene profiles to better predict the prognosis and efficiency of immune checkpoint blockade therapies (ICBs). Methods We retrieved transcriptome data across 420 OC and 88 normal tissue samples using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively. An external validation dataset containing 185 OC samples was downloaded from the Gene Expression Omnibus (GEO) database. Knockdown and pathway prediction of B4GALT5 were conducted to investigate the function and mechanism of B4GALT5 in OC proliferation, migration and invasion. Results A total of 50 differentially expressed GT genes were identified between OC and normal ovarian tissues. Two clusters were stratified by operating consensus clustering, but no significant prognostic value was observed. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 6-gene signature was built that classified OC patients in the TCGA cohort into a low- or high-risk group. Patients with high scores had a worse prognosis than those with low scores. This risk signature was further validated in an external GEO dataset. Furthermore, the risk score was an independent risk predictor, and a nomogram was created to improve the accuracy of prognostic classification. Notably, the low-risk OC patients exhibited a higher degree of antitumor immune cell infiltration and a superior response to ICBs. B4GALT5, one of six hub genes, was identified as a regulator of proliferation, migration and invasion in OC. Conclusion Taken together, we established a reliable GT-gene-based signature to predict prognosis, immune status and identify OC patients who would benefit from ICBs. GT genes might be a promising biomarker for OC progression and a potential therapeutic target for OC.

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“…The I antigen may enhance NK cell killing of leukemia cells. 30 Leukemia cell lines that strongly express I antigen were more sensitive to NK cell cytotoxicity. Moreover, transfecting cells with GCNT2 can increase NK cell cytotoxicity nearly twofold.…”

Section: Gcnt2 and Leukocytesmentioning

confidence: 99%

An update on the I blood group system

Cooling

2019

Immunohematology

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This update of the I blood group system (Cooling L. Polylactosamines, there's more than meets the "Ii": a review of the I system. Immunohematology 2010;26:133-55) continues to show the Ii antigens to be increasingly recognized as important posttranslational modifiers regulating cell adhesion, signaling, differentiation, and cancer. Ii antigens can modulate the immune response through the galectin lattice, as well as influence specific protein-protein interactions. Changes in GCNT2 and I expression accompany stem cell differentiation and are associated with tumor progression in melanoma and breast and colon cancer. Regulation of GCNT2 expression varies between cell types and differentiation. In red blood cell differentiation, GCNT2 is regulated by methylation, microRNAs, and mitogen-activated protein kinase signaling pathways. Methylation and microRNAs also play a prominent role in altering GCNT2 expression in several epithelial cancers. In congenital cataracts, GCNT2 mutations may account for 4-6 percent of all cases. GCNT2 may be particularly susceptible to gene deletion and rearrangements due to the density of Alu-repeat elements. Immunohematology 2019;35:85-90.

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

Abstract: 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.

Cited by 4 publications

References 41 publications

A Developed NK-92MI Cell Line with Siglec-7neg Phenotype Exhibits High and Sustainable Cytotoxicity against Leukemia Cells

A Developed NK-92MI Cell Line with Siglec-7neg Phenotype Exhibits High and Sustainable Cytotoxicity against Leukemia Cells

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer

An update on the I blood group system

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