Demethylating agent 5-aza-2′-deoxycytidine activates HLA-G expression in human leukemia cell lines

Poláková, K; Bandžuchová, E; Kuba, Daniel; Russ, G

doi:10.1016/j.leukres.2008.08.003

Cited by 29 publications

(17 citation statements)

References 27 publications

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“…19 In accordance with these reports, we showed here that 5-AZA treatment of tumor cell lines increased HLA-G protein expression and subsequently enhanced HLA-G 26-40 -specific T cell responses. Interestingly, 5-AZA treatment did not upregulate the expression levels of HLA-G on the tumor cell surface, indicating that the production of the HLA-G 26-40 peptide epitope via antigen processing does not require protein cell surface expression.…”

Section: Discussionsupporting

confidence: 92%

“…[15][16][17] Epigenetic factors such as DNA methylation are involved in the regulation of HLA-G expression and demethylating agents such as 5-aza-2 0 -deoxycytidine (5-AZA) can enhance HLA-G expression in leukemias. 18,19 Because of its immune-suppressive activity and its tissue-restricted expression, it is possible that HLA-G could function as a TAA for developing T cell-based immunotherapy. Here, we report that HLA-G specific, MHC class II (MHC-II)-restricted, tumor-reactive CD4 C HTL responses can be generated in both healthy donors and cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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(2016) Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy, OncoImmunology, 5:6, e1169356 ABSTRACTTumor 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 C helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8 C 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-G 26-40 was effective in eliciting tumor-reactive CD4 C T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2 0 -deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G 26-40 -specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Treatment of a HLA-G-negative melanoma cell line with 5azaC restored HLA-G expression; similarly 5azaC activated HLA-G expression in human leukemia cell lines, even in malignant hematopoietic cells isolated from patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (B-CLL) (Polakova et al, 2009a;Polakova et al, 2009b). Further research found that HLA-G was silenced as a result of CpG hypermethylation within a 5′ regulatory region upstream of the start codon (Moreau et al, 2003;Yan et al, 2005).…”

Section: Hla-ligand Of Kirmentioning

confidence: 97%

Transcription Regulation and Epigenetic Control of Expression of Natural Killer Cell Receptors and Their Ligands

Zhou¹,

Zhang²,

Zhang³

et al. 2011

Advances in Cancer Therapy

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“…These observations strongly suggest that decitabine has prospective therapeutic implications for specific immunotherapy against human tumors. However, a human non-classical HLA class I antigen HLA-G expression appears to be tightly regulated by decitabine [79]. HLA-G antigen exhibits immune-tolerant properties and its expression in tumors may contribute to tumor immune escape.…”

Section: Restoring the Expression Of Hla Class I Antigensmentioning

confidence: 99%

Decitabine: a promising epi-immunotherapeutic agent in solid tumors

Mei

Nie

et al. 2015

Expert Review of Clinical Immunology

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The incidence of malignancies is increasing worldwide. Despite early detection, surgical resection, chemotherapy and radiotherapy, numerous patients continue to die from metastasis or recurrence. The immune system has the capacity to eradicate cancer cells; however, many tumors, especially solid tumors, present considerable challenges that render immune cells ineffectual, making cancer cells almost 'invisible' to the immune system. Compelling evidence has demonstrated that DNA methylation is involved in tumor development and progression, leading to the impaired immunogenicity and immune recognition of cancer cells. The hypomethylating agent decitabine has been shown to have therapeutic effects in malignancies and exhibits an effective immune efficacy in eliminating cancer cells. Based on the hypomethylating and immune remodeling effects of decitabine, we propose in this review that decitabine can be considered an epi-immunotherapeutic agent. We summarize the results of recent preclinical studies and clinical trials for decitabine and discuss the connections among its hypomethylating effect, immune-activated mechanisms and clinical activity in solid tumors, keeping in mind the goal of optimizing dosing schedules.

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Demethylating agent 5-aza-2′-deoxycytidine activates HLA-G expression in human leukemia cell lines

Cited by 29 publications

References 27 publications

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

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

Transcription Regulation and Epigenetic Control of Expression of Natural Killer Cell Receptors and Their Ligands

Decitabine: a promising epi-immunotherapeutic agent in solid tumors

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