Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy. (2nd June 2016)

• Record Type: Journal Article
• Authors: Ishibashi, Kei; Kumai, Takumi; Ohkuri, Takayuki; Kosaka, Akemi; Nagato, Toshihiro; Hirata, Yui; Ohara, Kenzo; Oikawa, Kensuke; Aoki, Naoko; Akiyama, Naoko; Sado, Masatoshi; Kitada, Masahiro; Harabuchi, Yasuaki; Celis, Esteban; Kobayashi, Hiroya
• Is Part Of: Oncoimmunology. Volume 5:Number 6(2016)
• Publication Date: 2016-06-02
• Subjects: Human leukocyte antigen G -- immune escape -- immunotherapy -- peptide vaccine -- 5-aza-2′-deoxycytidine; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1169356
• Languages: English
• ISSNs: 2162-402X

Abstract

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.