A Novel Tumor Antigen Derived from Enhanced Degradation of Bax Protein in Human Cancers

Nunes, Claudia Trindade; Miners, Kelly L.; Dolton, Garry; Pepper, Chris; Fegan, Christopher; Mason, Malcolm David; Man, Stephen

doi:10.1158/0008-5472.can-11-0393

Cited by 15 publications

(21 citation statements)

References 40 publications

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“…Additionally, the HLA-DRB1*0101 (HLA-DR1)-restricted CD4 + clone, Flu2C5, was used, which recognizes the PKYVKQNTLKLAT epitope from influenza A haemagglutinin (HA: residues 307–319) 25. T cell clones were routinely expanded by restimulation with allogeneic peripheral blood mononuclear cells (PBMCs) and phytohaemagglutinin (PHA), as described previously 26, then cultured for at least 2–3 weeks before being used for experimentation. Fresh heparinized blood was obtained from volunteers or via the Welsh Blood Service, with appropriate ethical approval.…”

Section: Methodsmentioning

confidence: 99%

Comparison of peptide–major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells

Dolton

Lissina

Skowera

et al. 2014

Clinical and Experimental Immunology

104

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Fluorochrome-conjugated peptide–major histocompatibility complex (pMHC) multimers are widely used for flow cytometric visualization of antigen-specific T cells. The most common multimers, streptavidin–biotin-based ‘tetramers’, can be manufactured readily in the laboratory. Unfortunately, there are large differences between the threshold of T cell receptor (TCR) affinity required to capture pMHC tetramers from solution and that which is required for T cell activation. This disparity means that tetramers sometimes fail to stain antigen-specific T cells within a sample, an issue that is particularly problematic when staining tumour-specific, autoimmune or MHC class II-restricted T cells, which often display TCRs of low affinity for pMHC. Here, we compared optimized staining with tetramers and dextramers (dextran-based multimers), with the latter carrying greater numbers of both pMHC and fluorochrome per molecule. Most notably, we find that: (i) dextramers stain more brightly than tetramers; (ii) dextramers outperform tetramers when TCR–pMHC affinity is low; (iii) dextramers outperform tetramers with pMHC class II reagents where there is an absence of co-receptor stabilization; and (iv) dextramer sensitivity is enhanced further by specific protein kinase inhibition. Dextramers are compatible with current state-of-the-art flow cytometry platforms and will probably find particular utility in the fields of autoimmunity and cancer immunology.

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Section: Methodsmentioning

confidence: 99%

Comparison of peptide–major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells

Dolton

Lissina

Skowera

et al. 2014

Clinical and Experimental Immunology

104

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“…Bax is one of the pro-apoptotic genes, the overexpression of which results in apoptosis in a number of cells [32]. Bax expression seems to play a critical role in suppressing the development of cancer, and the decrease in Bax expression has been found in lots of cancers [33]. The apoptosis-related proteins, such as caspase3 and p53 could interact with NGAL [34,35].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Downregulation of NGAL is Required for the Inhibition of Proliferation and the Promotion of Apoptosis of Human Gastric Cancer MGC-803 Cells

Han

Nie

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gastric cancer is considered as a common malignancy with a poor prognosis as well as unsatisfactory treatment. Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to affect multiple aspects of human tumor, including gastric cancer. This study aims to explore the effects of NGAL gene silencing on the proliferation as well as apoptosis of human gastric cancer MGC-803 cells. Methods: This study included 87 patients with gastric cancer. MGC-803 cells were collected and mainly treated with siRNA against NGAL and recombinant NGAL plasmid. The expression of NGAL mRNA and the expressions of NGAL protein and apoptosis-related proteins were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Cell cycle and apoptosis were tested by flow cytometry, and cell proliferation was detected by water soluble tetrazolium-1 (WST-1) assay. The effect of NGAL gene silencing on tumorigenicity of MGC-803 cells in vivo was detected through establishment of xenograft in nude mice. Results: NGAL was highly expressed in gastric cancer tissues. The protein and mRNA expressions of NGAL gene in MGC-803 cells treated with NGAL-siRNA were obviously reduced, and the amount of cells in G0/G1 phase was increased. Moreover, MGC-803 cells treated with NGAL-siRNA exhibited inhibited proliferation, enhanced apoptosis, decreased expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) as well as B-cell lymphoma-2 (Bcl-2) and increased expressions of cysteine-aspartic acid specific protease-9 (caspase-9) and Bcl2-associated X (Bax), as well as repressed tumorigenicity in vivo. Conclusion: NGAL gene silencing inhibits proliferation and promotes apoptosis of MGC-803 cells, which can provide a novel theory for treatment of gastric cancer.

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“…Many different TAAs have been described [27,28,29]; so far the research has mainly focused on six different HCC-associated antigens: α-fetoprotein (AFP), glypican-3 (GPC-3), NY-ESO-1, SSX-2, melanoma antigen gene-A (MAGE-A), and human telomerase-reverse transcriptase (hTERT). …”

Section: Taa-specific Cd8+ T-cell Immune Responsesmentioning

confidence: 99%

Cellular Immune Responses to Hepatocellular Carcinoma: Lessons for Immunotherapy

Schmidt

Neumann‐Haefelin

Thimme³

2012

Dig Dis

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a continuously high mortality. Thus, the development of new therapeutic strategies is crucial to decrease recurrence rates and to improve the overall survival rates of HCC patients. The rationale for immunotherapy is based on the findings of several studies showing specific CD8⁺ T-cell responses against various tumor-associated antigens (TAAs) in HCC patients and a clinical benefit of T-cell infiltration in the tumor tissue. However, the impact of TAA-specific CD8⁺ T-cell responses on tumor control seems to be rather weak. Several different mechanisms contribute to the failure of the cellular immune response and will be summarized in this review. The aim of immune-based therapies is to overcome these mechanisms of T-cell failure and to induce or boost TAA-specific CD8⁺ and CD4⁺ T-cell responses. Several preclinical and clinical studies of immune-based therapeutic approaches show encouraging results and will be discussed in this review.

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A Novel Tumor Antigen Derived from Enhanced Degradation of Bax Protein in Human Cancers

Cited by 15 publications

References 40 publications

Comparison of peptide–major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells

Comparison of peptide–major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells

Downregulation of NGAL is Required for the Inhibition of Proliferation and the Promotion of Apoptosis of Human Gastric Cancer MGC-803 Cells

Cellular Immune Responses to Hepatocellular Carcinoma: Lessons for Immunotherapy

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