Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin

Nakatsugawa, Munehide; Horie, Kazutaka; Yoshikawa, Toshiaki; Shimomura, Manami; Kikuchi, Yuto; Sakemura, Noriko; Suzuki, Shiro; Nobuoka, Daisuke; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Harada, Kenji; Takasu, Hideo; Sato, Noriyuki; Nakatsura, Tetsuya

doi:10.3892/ijo.2011.1089

Cited by 7 publications

(8 citation statements)

References 40 publications

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“…LGSN , located on chromosome 6q12, encodes a glutamine synthetase I family protein, called lengsin, that was previously reported to be a constitutive lens‐specific protein but without the glutaminase activity . Recently, lengsin was identified as a novel tumor‐associated antigen and revealed its essential role in cell survival . In the present study, we found that CM patients with genotypes of LGSN rs12663017 TA + AA had a better CMSS.…”

Section: Discussionsupporting

confidence: 60%

“…42 Recently, lengsin was identified as a novel tumor-associated antigen and revealed its essential role in cell survival. 42,43 In the present study, we found that CM patients with LGSN rs12663017, and (c) NOXRED1 rs8012548 in the additive model; (B) the eQTL from the GTEx project using the additive model for HAL rs17676826 in skin tissues from sun-exposed lower leg skin (a) and sun-not-exposed suprapubic (b), NOXRED1 rs8012548 in skin tissues from sun-exposed lower leg (c), and sun-not-exposed suprapubic (d), LGSN rs12663017 in the whole blood (e), and NOXRED1 rs8012548 in subcutaneous adipose (e family. 44 In general, glutamine is degraded to glutamate, which then can consecutively be converted to proline by PYCR.…”

Section: Discussionmentioning

confidence: 99%

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Genetic variants in glutamine metabolic pathway genes predict cutaneous melanoma‐specific survival

Chen

Liu

et al. 2019

Molecular Carcinogenesis

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Glutamine dependence is a unique metabolic defect seen in cutaneous melanoma (CM), directly influencing the treatment and prognosis. Here, we investigated the associations between 6025 common single‐nucleotide polymorphisms (SNPs) in 77 glutamine metabolic pathway genes with CM‐specific survival (CMSS) using genotyping datasets from two published genome‐wide association studies (GWASs). In the single‐locus analysis, 76 SNPs were found to be significantly associated with CMSS (P < .050, false‐positive report probability < 0.2 and Bayesian false discovery probability < 0.8) in the discovery dataset, of which seven SNPs were replicated in the validation dataset and three SNPs (HAL rs17676826T > C, LGSN rs12663017T > A, and NOXRED1 rs8012548A > G) independently predicted CMSS, with an effect‐allele attributed adjusted hazards ratio of 1.52 (95% confidence interval = 1.19‐1.93) and P < .001, 0.68 (0.54‐0.87) and P = .002 and 0.62 (0.46‐0.83) and P = .002, respectively. The model including the number of unfavorable genotypes (NUGs) of these three SNPs and covariates improved the five‐year CMSS prediction (P = .012) than the one with other covariates only. Further expression quantitative trait loci (eQTL) analysis found that the LGSN rs12663017 A allele was significantly associated with increased messenger RNA (mRNA) expression levels (P = 8.89 × 10 −11) in lymphoblastoid cell lines of the 1000 Genomes Project database. In the analysis of the genotype tissue expression (GTEx) project datasets, HAL rs17676826 C and NOXRED1 rs8012548 G alleles were significantly associated with their mRNA expression levels in sun‐exposed skin of the lower leg (P = 6.62 × 10−6 and 1.37 × 10−7, respectively) and in sun‐not‐exposed suprapubic skin (P < .001 and 1.43 × 10−8, respectively). Taken together, these genetic variants of glutamine‐metabolic pathway genes may be promising predictors of survival in patients with CM.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Genetic variants in glutamine metabolic pathway genes predict cutaneous melanoma‐specific survival

Chen

Liu

et al. 2019

Molecular Carcinogenesis

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“…2) suggested that mGPC3-1 could induce peptide-specific CTLs. In addition, antigen-derived and CTL-inducible peptides are not necessarily presented by cancer cells endogenously expressing the antigen (23,30). Hence, we confirmed whether the mGPC3-1 peptide-specific CTL line could recognize RMA-GPC3-puro endogenously expressing mGPC3 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the binding affinity of the predicted peptides to H2-K b or H2-D b molecules, an in vitro cellular binding assay was performed as previously reported (23,26). Briefly, after incubation of RMA-S cells in culture medium at 26°C overnight, cells (1×10 6 ) were washed with PBS and suspended in 100 μ l Opti-MEM ® (Invitrogen) with or without 10 μ g peptide, followed by incubation at 26°C for 3 h and then at 37°C for 3 h. After washing with PBS, H2-K b or H2-D b expression was measured with a BD FACSCanto™ II flow cytometer (BD) using FITC-conjugated H2-K b (BioLegend Inc., AF6-88.5) or H2-D b (BioLegend Inc., KH95) specific monoclonal antibody and mean fluorescence intensity (MFI) was recorded.…”

Section: Methodsmentioning

confidence: 99%

Identification of an H2-Kb or H2-Db restricted and glypican-3-derived cytotoxic T-lymphocyte epitope peptide

Iwama

Horie

Yoshikawa

et al. 2013

International Journal of Oncology

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Glypican-3 (GPC3) is overexpressed in human hepatocellular carcinoma (HCC) but not expressed in normal tissues except for placenta and fetal liver and therefore is an ideal target for cancer immunotherapy. In this study, we identified an H2-Kb or H2-Db restricted and murine GPC3 (mGPC3)-derived cytotoxic T-lymphocyte (CTL) epitope peptide in C57BL/6 (B6) mice, which can be used in the design of preclinical studies of various therapies with GPC3-target immunotherapy in vivo. First, 11 types of 9- to 10-mer peptides predicted to bind with H2-Kb or H2-Db were selected from the mGPC3 amino acid sequence based on the binding score as calculated by the BIMAS software. We evaluated the peptide-binding affinity and confirmed that all peptides were able to bind to H2-Kb or H2-Db by in vitro cellular binding assay. Subsequently, a mixed peptide vaccine and single peptide vaccine were given to B6 mice to evaluate immunogenic potential of the 11 selected peptides. Using the splenocytes from peptide-vaccinated mice, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assays showed that mGPC3-1127–136 (AMFKNNYPSL) peptide was the most efficient for inducing CTLs among the 11 peptides. Next, we demonstrated that the mGPC3-1 peptide-specific CTL line could recognize mGPC3-expressing cancer cells, suggesting that mGPC3-1 peptide was an endogenously presented peptide. In conclusion, we identified mGPC3-1 as an H2-Kb or H2-Db restricted, mGPC3-derived CTL epitope peptide.

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“…Activated CTLs play an important role in the antitumor immunological response by specifically recognizing and subsequently killing tumor cells expressing TAAs (1,2). Dozens of TAAs have been newly identified and well described in recent years (3)(4)(5)(6). However, the expression of most TAAs are restricted to a few tumor types and to a fraction of patients with these types of tumors (7)(8)(9)(10), and the appearance of antigen-loss or antigen-alteration mutations in tumor cells in response to immune pressure has also been highlighted and extensively elucidated by many researchers (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Peptide FLNPDVLDI of heparanase is a novel HLA-A2-restricted CTL epitope and elicits potent immunological antitumor effects in vitro with an 8-branched design

et al. 2013

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The aim of this study was to predict and characterize a novel HLA-A2-restricted T-cell epitope of the human heparanase (HPSE) protein, as well as to evaluate its antitumor immunological effects in vitro with an 8-branched multiple antigenic peptide (MAP) design. The amino acid sequence of HPSE was scanned, and the cytotoxic T lymphocyte (CTL) epitopes were predicted using HLA-A2-restricted epitope-predictive algorithms based on supermotif and quantitative motif methods. The affinity of candidate peptides to HLA-A2 was evaluated using peptide-binding assay, by virtue of the characteristics of T2 cells. The MAPs consisting of the selected peptides were synthesized using an 8-branched design. The specific CTL-inducing ability of the MAPs was assessed by LDH release assay, and the CTL activity was evaluated by INF-γ ELISPOT assay. Among the predicted nonapeptides, the FLNPDVLDI peptide of HPSE showed the highest affinity to the HLA-A2 molecule. The 8-branched MAP comprising FLNPDVLDI induced specific CTLs for human HPSE in vitro, which effectively secreted IFN-γ and potently lysed HCC97-H human hepatocarcinoma cells and SW-480 human colonic carcinoma cells. The nonapeptide FLNPDVLDI of human HPSE appears to be a novel HLA-A2-restricted CTL epitope, and its 8-branch designed MAP is capable of inducing a potent HPSE-specific CTL response against tumor cells in vitro. Our study provides theoretical evidence for the peptide-based antitumor immunotherapy.

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Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin

Cited by 7 publications

References 40 publications

Genetic variants in glutamine metabolic pathway genes predict cutaneous melanoma‐specific survival

Genetic variants in glutamine metabolic pathway genes predict cutaneous melanoma‐specific survival

Identification of an H2-Kb or H2-Db restricted and glypican-3-derived cytotoxic T-lymphocyte epitope peptide

Peptide FLNPDVLDI of heparanase is a novel HLA-A2-restricted CTL epitope and elicits potent immunological antitumor effects in vitro with an 8-branched design

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