論文 - 詳細
| RRC ID | 19311 |
|---|---|
| 著者 | Hambach L, Ling KW, Pool J, Aghai Z, Blokland E, Tanke HJ, Bruijn JA, Halfwerk H, van Boven H, Wieles B, Goulmy E. |
| タイトル | Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy. |
| ジャーナル | Blood |
| Abstract |
Clinical responses of solid tumors after allogeneic human leukocyte antigen-matched stem cell transplantation (SCT) often coincide with severe graft-versus-host disease (GVHD). Targeting minor histocompatibility antigens (mHags) with hematopoiesis- and cancer-restricted expression, for example, HA-1, may allow boosting the antitumor effect of allogeneic SCT without risking severe GVHD. The mHag HA-1 is aberrantly expressed in cancers of most entities. However, an estimated 30% to 40% of solid tumors do not express HA-1 (ie, are HA-1(neg)) and cannot be targeted by HA-1-specific immunotherapy. Here, we investigated the transcriptional regulation of HA-1 gene expression in cancer. We found that DNA hypermethylation in the HA-1 promoter region is closely associated with the absence of HA-1 gene expression in solid tumor cell lines. Moreover, we detected HA-1 promoter hypermethylation in primary cancers. The hypomethylating agent 5-aza-2'-deoxycytidine induced HA-1 expression only in HA-1(neg) tumor cells and sensitized them for recognition by HA-1-specific cytotoxic T lymphocytes. Contrarily, the histone deacetylation inhibitor trichostatin A induced HA-1 expression both in some HA-1(neg) tumor cell lines and in normal nonhematopoietic cells. Our data suggest that promoter hypermethylation contributes to the HA-1 gene regulation in tumors. Hypomethylating drugs might extend the safe applicability of HA-1 as an immunotherapeutic target on solid tumors after allogeneic SCT. |
| 巻・号 | 113(12) |
| ページ | 2715-22 |
| 公開日 | 2009-3-19 |
| DOI | 10.1182/blood-2008-05-158956 |
| PII | S0006-4971(20)37537-6 |
| PMID | 19096014 |
| MeSH | Acetylation / drug effects Antigens, Neoplasm / biosynthesis* Antigens, Neoplasm / genetics Antigens, Neoplasm / immunology Azacitidine / analogs & derivatives* Azacitidine / pharmacology Azacitidine / therapeutic use Cell Line, Tumor / drug effects Cell Line, Tumor / metabolism CpG Islands DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors DNA Methylation / drug effects* DNA, Neoplasm / drug effects* Decitabine Gene Expression Regulation, Neoplastic / drug effects* Gene Silencing / drug effects* Histones / metabolism Humans Hydroxamic Acids / pharmacology Immunotherapy / methods* Minor Histocompatibility Antigens / biosynthesis* Minor Histocompatibility Antigens / genetics Minor Histocompatibility Antigens / immunology Neoplasm Proteins / antagonists & inhibitors Neoplasm Proteins / metabolism Neoplasms / genetics* Neoplasms / immunology Neoplasms / pathology Oligopeptides / biosynthesis* Oligopeptides / genetics Oligopeptides / immunology Promoter Regions, Genetic / drug effects Promoter Regions, Genetic / genetics Protein Processing, Post-Translational / drug effects RNA, Messenger / biosynthesis RNA, Neoplasm / biosynthesis T-Lymphocytes, Cytotoxic / immunology Transcription, Genetic |
| IF | 17.794 |
| 引用数 | 31 |
| WOS 分野 | HEMATOLOGY |
| 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 | Wikipedia |
| 各媒体での言及数の合計 | 6 |
| 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 | OCUB-F(RCB0882) |