QPY/RAH haplotypes of the GZMB gene are associated with natural killer cell cytotoxicity

Oboshi, Wataru; Watanabe, Tôru; Hayashi, Keisuke; Nakamura, Takehiro; Yukimasa, Nobuyasu

doi:10.1007/s00251-017-1014-6

Cited by 10 publications

(10 citation statements)

References 45 publications

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“…Similar to their murine counterparts, individuals with these GZMB mutations also develop normally, and conventional T cells from these individuals exhibited full killing capacity against transformed B cells. However, other studies indicated that R 48 A 88 H 245 patient-derived NK and gd T cells had reduced killing capacity against other tumor cell types (18,19). These data suggest that granzyme functional redundancy may depend on immune cell type or target cell type specific in humans.…”

Section: Granzymes In Cell Death and Diseasementioning

confidence: 86%

Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease

et al. 2021

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CD4 T cells play important roles in promoting protective immunity and autoimmune disease. A great deal of attention has been given to the differentiation and function of subsets of cytokine-producing CD4 T cells (i.e., Th1, Th2, and Th17 cells) in these settings. However, others have also observed the accumulation of granzyme-producing CD4 T cells in tumors and in autoimmune patients that are distinct from their cytokine-producing counterparts. Despite the relatively large numbers of granzyme-producing cells in diseased tissues, their roles in driving disease have remained enigmatic. This review will focus on the phenotype(s) and roles of granzymeproducing CD4 T cells in cancer and autoimmunity. We will also examine how granzyme-producing cells interact with current therapeutics and speculate how they may be targeted during disease. ImmunoHorizons, 2021, 5: 909-917.

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Section: Granzymes In Cell Death and Diseasementioning

confidence: 86%

Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease

et al. 2021

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“…GZMB is one of the most potent cytotoxic molecules, which mainly has an anti-tumor effect in the TME. 46 , 47 CD8 + T cells with high expression of GZMB were shown to be associated with prolonged survival of osteosarcoma patients. 48 ITGA1 was shown to be is a malignant biomarker in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 98%

ATG16L1 is a Potential Prognostic Biomarker and Immune Signature for Osteosarcoma: A Study Based on Bulk RNA and Single-Cell RNA-Sequencing

Qin¹,

Luo²,

Y³

et al. 2022

IJGM

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Background Osteosarcoma is a common solid malignancy of the bone in children and adolescents, and its metastasis and recurrence are the principal causes of poor treatment outcomes. Methods Autophagy-related genes were used to cluster osteosarcoma patients by consensus clustering analysis using the GSE21257 database. Differentially expressed genes (DEGs) were identified by limma package. Multiple-gene risk signature was constructed using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression analyses. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine gene expression levels. Then, single-cell RNA-sequencing dataset GSE152048 were used to identify the correlation between the DEGs and effector molecules expressed in specific tumor-infiltrating immune cells. Results Two clusters were identified in the consensus clustering analysis, which were confirmed by principal component analysis. Limma analysis revealed that 15 genes were related, and 9 genes were screened using protein-protein interaction network and LASSO regression analysis. Cox regression analyses identified 5 genes. Combined with survival analysis, only the autophagy related 16 like 1 gene ( ATG16L1 ) was significant. The results of qRT-PCR showed low expression levels of ATG16L1 in tumor cells group. Immune infiltration analysis revealed significantly lower expression of CD8 + T cells in the high ATG16L1 gene expression group. ScRNA-seq revealed that in the ATG16L1 + CD8 + T cell group, the expression of GZMB was lower, whereas the expression of ITGA1 was higher. These results showed that ATG16L 1 is an immune-related gene, which is associated with poor prognosis in patients with osteosarcoma. Conclusion ATG16L1 is a potential prognostic biomarker and immune signature and may be a therapeutic target for osteosarcoma.

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“…However, they found no frequent linkage disequilibrium in a European population, which consisted of rs8192917, rs11539752, and rs2236338.In addition, rs8192917 has been reported in many studies. Oboshi et al 21 have shown that rs8192917 affected NK cell cytotoxicity. Yentur et al 22 reported that rs8192917 was associated with subacute sclerosing panencephalitis in patients infected with measles.…”

Section: Discussionmentioning

confidence: 99%

Association of GZMB polymorphisms and susceptibility to non-segmental vitiligo in a Korean population

Jeong

Kim

Seo

et al. 2021

Sci Rep

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Non-segmental vitiligo (NSV) is the most common type of vitiligo, which is characterized by chronic and progressive loss of melanocytes. Genetic factors have been shown to play a key role in NSV in association and family studies. Granzyme B is a serine protease found in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells that play an important role in inducing apoptotic changes of target cells. Several recent studies have provided evidence that polymorphism in the GZMB gene might be associated with autoimmune disease. A total of 249 NSV patients and 455 healthy controls were recruited to determine whether single nucleotide polymorphisms (SNPs) [rs2236337 (3′ untranslated region, UTR), rs2236338 (Tyr247His), rs11539752 (Pro94Ala), rs10909625 (Lys80Lys), rs8192917 (Arg55Gln), and rs7144366 (5′ near gene)] in GZMB gene contribute to the risk of developing NSV. Genotyping was performed using a single 192.24 Dynamic Array IFC. Data were analyzed using EP1 SNP Genotyping Analysis software to obtain genotype calls. Among the six SNPs tested, five SNPs (rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917) showed significant association with NSV susceptibility. Among them, rs2236338, rs11539752, rs10909625, and rs8192917 remained a statistically significant association following multiple correction test. The five SNPs were located within a block of linkage disequilibrium. Haplotypes T–A–G–T–T and C–G–C–C–C consisting of rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917 demonstrated significant association with NSV. Our results suggest that GZMB polymorphisms are associated with the development of NSV.

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QPY/RAH haplotypes of the GZMB gene are associated with natural killer cell cytotoxicity

Cited by 10 publications

References 45 publications

Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease

Granzyme-Producing CD4 T Cells in Cancer and Autoimmune Disease

ATG16L1 is a Potential Prognostic Biomarker and Immune Signature for Osteosarcoma: A Study Based on Bulk RNA and Single-Cell RNA-Sequencing

Association of GZMB polymorphisms and susceptibility to non-segmental vitiligo in a Korean population

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