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Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy

2016; Landes Bioscience; Volume: 5; Issue: 6 Linguagem: Inglês

10.1080/2162402x.2016.1169356

2162-402X

Kei Ishibashi, Takumi Kumai, Takayuki Ohkuri, Akemi Kosaka, Toshihiro Nagato, Yui Hirata, Kenzo Ohara, Kensuke Oikawa, Naoko Aoki, Naoko Akiyama, Masatoshi Sado, Masahiro Kitada, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi,

Immunotherapy and Immune Responses

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.