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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1169356
JournalOncoImmunology
Volume5
Issue number6
DOIs
StatePublished - Jun 2 2016

Fingerprint

Neoplasm Antigens
HLA Antigens
Epigenomics
Immunotherapy
T-Lymphocytes
decitabine
Methyltransferases
Neoplasms
Helper-Inducer T-Lymphocytes
Immune System
Tumor Escape
DNA
Cytotoxic T-Lymphocytes
Fetus
Breast Neoplasms
Peptides

Keywords

  • 5-aza-2′-deoxycytidine
  • Human leukocyte antigen G
  • immune escape
  • immunotherapy
  • peptide vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

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

In: OncoImmunology, Vol. 5, No. 6, e1169356, 02.06.2016.

Research output: Contribution to journalArticle

Ishibashi, K, Kumai, T, Ohkuri, T, Kosaka, A, Nagato, T, Hirata, Y, Ohara, K, Oikawa, K, Aoki, N, Akiyama, N, Sado, M, Kitada, M, Harabuchi, Y, Celis, E & Kobayashi, H 2016, 'Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy', OncoImmunology, vol. 5, no. 6, e1169356. https://doi.org/10.1080/2162402X.2016.1169356
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. / Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy. In: OncoImmunology. 2016 ; Vol. 5, No. 6.
@article{afe34e8e35db4d0092836ba76b9bedc1,
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.",
keywords = "5-aza-2′-deoxycytidine, Human leukocyte antigen G, immune escape, immunotherapy, peptide vaccine",
author = "Kei Ishibashi and Takumi Kumai and Takayuki Ohkuri and Akemi Kosaka and Toshihiro Nagato and Yui Hirata and Kenzo Ohara and Kensuke Oikawa and Naoko Aoki and Naoko Akiyama and Masatoshi Sado and Masahiro Kitada and Yasuaki Harabuchi and Esteban Celis and Hiroya Kobayashi",
year = "2016",
month = "6",
day = "2",
doi = "10.1080/2162402X.2016.1169356",
language = "English (US)",
volume = "5",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "6",

}

TY - JOUR

T1 - Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy

AU - Ishibashi, Kei

AU - Kumai, Takumi

AU - Ohkuri, Takayuki

AU - Kosaka, Akemi

AU - Nagato, Toshihiro

AU - Hirata, Yui

AU - Ohara, Kenzo

AU - Oikawa, Kensuke

AU - Aoki, Naoko

AU - Akiyama, Naoko

AU - Sado, Masatoshi

AU - Kitada, Masahiro

AU - Harabuchi, Yasuaki

AU - Celis, Esteban

AU - Kobayashi, Hiroya

PY - 2016/6/2

Y1 - 2016/6/2

N2 - 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.

AB - 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.

KW - 5-aza-2′-deoxycytidine

KW - Human leukocyte antigen G

KW - immune escape

KW - immunotherapy

KW - peptide vaccine

UR - http://www.scopus.com/inward/record.url?scp=84976272189&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976272189&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2016.1169356

DO - 10.1080/2162402X.2016.1169356

M3 - Article

VL - 5

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 6

M1 - e1169356

ER -