TY - JOUR
T1 - Identification of novel HLA-A∗24:02-restricted epitope derived from a homeobox protein expressed in hematological malignancies
AU - Matsushita, Maiko
AU - Otsuka, Yohei
AU - Tsutsumida, Naoya
AU - Tanaka, Chiaki
AU - Uchiumi, Akane
AU - Ozawa, Koji
AU - Suzuki, Takuma
AU - Ichikawa, Daiju
AU - Aburatani, Hiroyuki
AU - Okamoto, Shinichiro
AU - Kawakami, Yutaka
AU - Hattori, Yutaka
N1 - Publisher Copyright:
© 2016 Matsushita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0146371
DO - 10.1371/journal.pone.0146371
M3 - Article
C2 - 26784514
AN - SCOPUS:84958205852
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 1
M1 - e0146371
ER -
