論文 - 詳細
| RRC ID | 81665 |
|---|---|
| 著者 | Tamai T, Mizukoshi E, Kumagai M, Terashima T, Iida N, Kitahara M, Shimakami T, Kitamura K, Arai K, Yamashita T, Sakai Y, Yamashita T, Honda M, Fushimi K, Kaneko S. |
| タイトル | A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma. |
| ジャーナル | Sci Rep |
| Abstract |
α-Fetoprotein (AFP) is considered a good target for immunotherapy strategies against hepatocellular carcinoma (HCC); however, no immunodominant AFP-derived MHC class II-restricted helper T-lymphocyte (HTL) epitope has been reported. Therefore, we identified novel AFP-derived HTL epitopes possessing high immunogenicity. HTL epitopes were predicted using the online service, and peptides were subsequently synthesized. Four newly synthesized peptides showed positive reactivity in >20% patients on ELISPOT using peripheral blood mononuclear cells (PBMCs). Among these, the highest rate was shown by AFP1 (MKWVESIFLIFLLNFTESRT), which also showed the highest positive rate in cell proliferation assays. Binding assays demonstrated that AFP1 had strong binding properties toward MHC molecules. Further, blocking assays performed using an anti-HLA-DR antibody showed that immune response decreased, confirming the binding of AFP1 to HLA-DR molecules. Furthermore, the survival rates of patients with stages II-IV HCC indicated that T cell response against AFP1 led to significantly greater survival that of patients without T cell response. When evaluating immune response against AFP1 before and after HCC treatment, an increase in the frequency of peptide-specific T cells was observed after treatment in patients with HLA-DRB1*1502, *0405, and *0901 alleles. In conclusion, the identified epitopes may be useful for immunotherapy strategies against HCC. |
| 巻・号 | 10(1) |
| ページ | 4021 |
| 公開日 | 2020-3-4 |
| DOI | 10.1038/s41598-020-60843-4 |
| PII | 10.1038/s41598-020-60843-4 |
| PMID | 32132566 |
| PMC | PMC7055302 |
| MeSH | Adult Aged Aged, 80 and over Carcinoma, Hepatocellular / immunology* Carcinoma, Hepatocellular / pathology Epitopes, T-Lymphocyte / immunology* Female Humans Immunity, Cellular Liver Neoplasms / immunology* Liver Neoplasms / pathology Male Middle Aged Neoplasm Proteins / immunology* Peptides / immunology* T-Lymphocytes / immunology T-Lymphocytes / pathology alpha-Fetoproteins / immunology* |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | EBV-infected human B-lymphocyte cell line |