Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies
The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukem...
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718592/ |
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pubmed-47185922016-01-30 Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies Matsushita, Maiko Otsuka, Yohei Tsutsumida, Naoya Tanaka, Chiaki Uchiumi, Akane Ozawa, Koji Suzuki, Takuma Ichikawa, Daiju Aburatani, Hiroyuki Okamoto, Shinichiro Kawakami, Yutaka Hattori, Yutaka Research Article The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2271-279). The CTLs induced by PEPP2271-279 recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2’-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2’-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients. Public Library of Science 2016-01-19 /pmc/articles/PMC4718592/ /pubmed/26784514 http://dx.doi.org/10.1371/journal.pone.0146371 Text en © 2016 Matsushita et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Matsushita, Maiko Otsuka, Yohei Tsutsumida, Naoya Tanaka, Chiaki Uchiumi, Akane Ozawa, Koji Suzuki, Takuma Ichikawa, Daiju Aburatani, Hiroyuki Okamoto, Shinichiro Kawakami, Yutaka Hattori, Yutaka |
| spellingShingle |
Matsushita, Maiko Otsuka, Yohei Tsutsumida, Naoya Tanaka, Chiaki Uchiumi, Akane Ozawa, Koji Suzuki, Takuma Ichikawa, Daiju Aburatani, Hiroyuki Okamoto, Shinichiro Kawakami, Yutaka Hattori, Yutaka Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies |
| author_facet |
Matsushita, Maiko Otsuka, Yohei Tsutsumida, Naoya Tanaka, Chiaki Uchiumi, Akane Ozawa, Koji Suzuki, Takuma Ichikawa, Daiju Aburatani, Hiroyuki Okamoto, Shinichiro Kawakami, Yutaka Hattori, Yutaka |
| author_sort |
Matsushita, Maiko |
| title |
Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies |
| title_short |
Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies |
| title_full |
Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies |
| title_fullStr |
Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies |
| title_full_unstemmed |
Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies |
| title_sort |
identification of novel hla-a*24:02-restricted epitope derived from a homeobox protein expressed in hematological malignancies |
| description |
The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2271-279). The CTLs induced by PEPP2271-279 recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2’-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2’-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718592/ |
| _version_ |
1613525781923758080 |