Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy
著者
石橋, 佳
(Ishibashi,Kei)
熊井, 琢美
(Kumai, Takumi)
大栗, 敬幸
(Ohkuri, Takayuki)
小坂, 朱
(Kosaka, Akemi)
長門, 利純
(Nagato, Toshihiro)
平田, 結
(Hirata, Yui)
大原, 賢三
(Ohara, Kenzo)
及川, 賢輔
(Oikawa, Kensuke)
青木, 直子
(Aoki, Naoko)
秋山, 直子
(Akiyama, Naoko)
佐渡, 正敏
(Sado, Masatoshi)
北田, 正博
(Kitada, Masahiro)
原渕, 保明
(Harabuchi, Yasuaki)
Esteban, Celis
小林, 博也
(Kobayashi, Hiroya)
上位タイトル
OncoImmunology
Vol.5,
No.6
(2016.
5)
識別番号
DOI
10.1080/2162402X.2016.1169356
その他
PMID：27471649
抄録
Tumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4+ helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8+ cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G26–40 was effective in eliciting tumor-reactive CD4+ T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G26–40-specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.
