Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin-2B in oral cancer patients

Kobayashi, Jun’ichi; Torigoe, Toshihiko; Hirohashi, Yoshihiko; Idenoue, Satomi; Miyazaki, Akira; Yamaguchi, Akira; Hiratsuka, Hiroyoshi; Sato, Noriyuki

doi:10.1186/1479-5876-7-1

Cited by 75 publications

(61 citation statements)

References 31 publications

(34 reference statements)

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“…Similar to other previous reports of China [10,14,26], our study showed that GJB2 mutations were an important cause of NSHL in Jiangsu deafness populations, and the most common GJB2 mutation detected in our study group was the c.235delC (102/658; 15.50% ). While the c.35delG mutation, which is prevalent in the Caucasians and rarely found in Chinese populations, was identified only in 2 patients.…”

Section: Discussionsupporting

confidence: 91%

“…Carrier frequencies of some mutational hot spots associated with NSHL from different areas and ethnic backgrounds have been reported [10-15], but the molecular etiology of NSHL in the Chinese Jiangsu Province population has not been investigated systematically. To further extend the epidemiological data of common gene mutations in Chinese population, we screened the GJB2 and mitochondrial 12S rRNA genes to determine the etiology of hearing loss in Jiangsu Province.…”

Section: Introductionmentioning

confidence: 99%

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Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China

et al. 2013

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BackgroundHearing loss is caused by several environmental and genetic factors and the proportion attributed to inherited causes is assumed at 50 ~ 60% . Mutations in GJB2 and mitochondrial DNA (mtDNA) 12S rRNA are the most common molecular etiology for nonsyndromic sensorineural hearing loss (NSHL). The mutation spectra of these genes vary among different ethnic groups.MethodsTo add the molecular etiologic information of hearing loss in the Chinese population, a total of 658 unrelated patients with NSHL from Jiangsu Province of China were selected for mutational screening including GJB2 and mtDNA 12S rRNA genes using PCR and DNA sequencing technology. As for controls, 462 normal-hearing individuals were collected.ResultsA total of 9 pathogenic mutations in the GJB2 and 7 pathogenic mutations in the 12S rRNA gene were identified. Of all patients, 70 had monoallelic GJB2 coding region mutation in the heterozygous state, 94 carried two confirmed pathogenic mutations including 79 homozygotes and 15 compound heterozygotes. The 235delC appears to be the most common deafness-causing GJB2 mutation (102/658, 15.50% ). No mutations or variants in the GJB2 exon1 and basal promoter region were found. In these patients, 4 subjects carried the m.1494C > T mutation (0.61% ) and 39 subjects harbored the m.1555A > G mutation (5.93% ) in mtDNA 12S rRNA gene. A novel sequence variant at m.1222A > G in the 12S rRNA gene was identified, which could alter the secondary structure of the 12S rRNA.ConclusionThe mutation spectrum and prevalence of GJB2 and mtDNA 12S rRNA genes in Jiangsu population are similar to other areas of China. There are in total 31.46% of the patients with NSHL carry deafness-causing mutation in GJB2 or mtDNA 12S rRNA genes. Mutation in GJB2 gene is the most common factor, mtDNA 12S rRNA also plays an important part in the pathogenesis of hearing loss in Jiangsu Province areas. The m.1222A > G was found to be a new candidate mutation associated with hearing loss. Our results indicated the necessity of genetic screening for mutations of these genes in Jiangsu patients with NSHL.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China

et al. 2013

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“…These phenomena should be attributed to the higher activity of aldehyde dehydrogenase in cancer cells 48-50. Alcohols or aldehydes were oxidized to the corresponding carboxylic acids in an alcohol dehydrogenase-independent pathway; carboxylic acids were further metabolized as precursors of the synthesis of cell membranes, which provide more substances to meet the rapid growth requirement of cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Identification of Volatile Biomarkers of Gastric Cancer Cells and Ultrasensitive Electrochemical Detection based on Sensing Interface of Au-Ag Alloy coated MWCNTs

Zhang¹,

Gao²,

Liu³

et al. 2014

Theranostics

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Successful development of novel electrochemical biosensing interface for ultrasensitive detection of volatile biomarkers of gastric cancer cells is a challenging task. Herein we reported to screen out novel volatile biomarkers associated with gastric cancer cells and develop a novel Au-Ag alloy composites-coated MWCNTs as sensing interface for ultrasensitive detection of volatile biomarkers. MGC-803 gastric cancer cells and GES-1 gastric mucous cells were cultured in serum-free media. The sample preparation approaches and HS-SPME conditions were optimized for screening volatile biomarkers. Volatiles emitted from the headspace of the cells/medium culture were identified using GC-MS. The Au-Ag nanoparticles-coated multiwalled carbon nanotubes were prepared as a sensing interface for detection of volatile biomarkers. Results showed that eight different volatile metabolites were screened out between MGC-803 cells and GES-1 cells. Two compounds such as 3-octanone and butanone were specifically present in the headspace of the MGC-803 cells. Three volatiles such as 4-isopropoxybutanol, nonanol and 4-butoxy 1-butanol coexisted in the headspace of both the MGC-803 cells and the GES-1 cells, their concentrations in the headspace of the GES-1cells were markedly higher than those in the MGC-803 cells, three volatiles such as formic acid propyl ester, 1.4-butanediol and 2, 6, 11-trimethyl dodecane solely existed in the headspace of the GES-1 cells. The nanocomposites of MWNTs loaded with Au-Ag nanoparticles were prepared as a electrochemical sensing interface for detection of two volatile biomarkers, cyclic voltammetry studies showed that the fabricated sensor could detect 3-octanone in the range of 0~0.0025% (v/v) and with a detection limitation of 0.3 ppb, could detect butanone in the range of 0 ~ 0.055% (v/v), and with a detection limitation of 0.5 ppb, and exhibited good selectivity. The novel electrochemical biosensor combined with volatile biomarkers of gastric cancer owns great potential in applications such as early diagnosis and the prognosis of gastric cancer in near future.

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“…The new amino-acid sequences generated in that case have previously shown to be potentially immunogenic. 27,28 Moreover, some of these epitopes produced by cancer-related alternative splicing are recognized by specific CD8 T cells [29][30][31][32] or CD4 T cells 33 from cancer patients. The presence of candidate antigens derived from alternative splicing has however never been described in B cell lymphomas.…”

Section: Discussionmentioning

confidence: 99%

CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes

Vauchy

Gamonet

Ferrand

et al. 2014

Intl Journal of Cancer

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Cancer-specific splice variants gain significant interest as they generate neo-antigens that could be targeted by immune cells. CD20, a membrane antigen broadly expressed in mature B cells and in B cell lymphomas, is subject to an alternative splicing named D393-CD20 leading to loss of membrane expression of the spliced isoform. D393-CD20 expression is detectable in transformed B cells and upregulated in various lymphoma B cells. In this study, we show that D393-CD20 is translated in malignant B cells and that D393-CD20 specific CD4 T cells producing IFN-c are present in B-cell lymphoma patients. Then, we have investigated whether the 20mer D393-CD20 peptide spanning the splicing site might be targeted by the immune system and we have shown that D393-CD20-specific CD4 Th1 clones could directly recognize malignant B cell lines and kill autologous lymphoma B cells indicating that D393-CD20-derived epitopes are naturally processed and presented on tumor cells. Finally, D393-CD20 peptide-based vaccination induced specific CD8 and CD4 T cell responses in HLA-humanized transgenic mice suggesting the presentation of D393-CD20 derived peptides on both HLA Class-I and -II. These findings support further investigations on the potential use of D393-CD20 directed specific immunotherapy in B cell malignancies.The effective discovery of clinically relevant tumor antigens holds a fundamental role for the development of new diagnostic tools and anticancer immunotherapies. Generally, tumor antigens are classified as unique antigens derived from point mutations or as shared antigens. The shared antigens are further divided into tumor-specific antigens, differentiation antigens and overexpressed antigens. The prioritization of cancer antigens is based on criteria such as immunogenicity, specificity, oncogenicity. 1 One mechanism that would lead to such priority targets could be alternative splicing. Alternative splicing can change the structure of mRNA by inclusion or skipping of exons, and this may alter the function, stability or binding properties of the encoded protein. 2 Aside from its role in physiological cell adaptation, alternative splicing has been shown to occur in human diseases, including cancer. 3 Particularly, the splice variants differ between cancer and normal corresponding tissues. 4,5 Cancerspecific splice variants are thus of significant interest as they may be involved in pathogenesis and may further potentially be used as biomarkers and generate novel targets for therapy. Because immune recognition of antigenic epitopes is highly specific, alternative exon splicing could provide the structural basis for expression of novel amino-acid sequences not subject to self repertoire tolerance.We previously identified an alternative transcript of the B cell lineage membrane receptor CD20. This alternative transcript lacks 168 nucleotides within Exon 3 to 7 compared to the wild-type CD20 transcript and referred thereafter as D393-CD20. 6 D393-CD20 translation gives rise to a protein lacking the extracellular domain and ...

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Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin-2B in oral cancer patients

Cited by 75 publications

References 31 publications

Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China

Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China

Identification of Volatile Biomarkers of Gastric Cancer Cells and Ultrasensitive Electrochemical Detection based on Sensing Interface of Au-Ag Alloy coated MWCNTs

CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes

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