title: Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy.
abstract: 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.
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan; Respiratory and Breast Center, Asahikawa Medical University Hospital, Asahikawa, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan; Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan; Cancer Immunology, Inflammation and Tolerance Program, Augusta University Cancer Center, Augusta, GA, USA.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kumai
authors.affiliation: Department of Pathology, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohkuri
authors.affiliation: Department of Pathology, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Kosaka
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan; Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan; Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Ohara
authors.affiliation: Department of Pathology, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.affiliation: Department of Pathology, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Aoki
authors.affiliation: Department of Surgical Pathology, Asahikawa Medical University Hospital , Asahikawa, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Akiyama
authors.affiliation: Department of Surgical Pathology, Asahikawa Medical University Hospital , Asahikawa, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Sado
authors.affiliation: Respiratory and Breast Center, Asahikawa Medical University Hospital , Asahikawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitada
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.affiliation: Cancer Immunology, Inflammation and Tolerance Program, Augusta University Cancer Center , Augusta, GA, USA.
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.affiliation: Department of Pathology, Asahikawa Medical University , Asahikawa, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
keywords: 5-aza-2′-deoxycytidine; Human leukocyte antigen G; immune escape; immunotherapy; peptide vaccine