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Characterization of HLA-G Regulation and HLA Expression in Breast Cancer and Malignant Melanoma Cell Lines upon IFN-γ Stimulation and Inhibition of DNA Methylation

IFN-γ 刺激和抑制 DNA 甲基化对乳腺癌和恶性黑色素瘤细胞系 HLA-G 调控和 HLA 表达的表征

  • 影响因子:4.32
  • DOI:10.3390/ijms21124307
  • 作者列表:"Nanna Jørgensen","Abid Sayed","Helene Bjerregaard Jeppesen","Gry Persson","Iben Weisdorf","Tina Funck","Thomas Vauvert Faurschou Hviid
  • 发表时间:2020-06-18
Abstract

The potential role of human leukocyte antigen (HLA)-G as a target for new cancer immunotherapy drugs has increased the interest in the analysis of mechanisms by which HLA-G expression is regulated, and how the expression can be manipulated. We characterized HLA expression in breast cancer and malignant melanoma cell lines and investigated the induction of HLA-G expression by two distinct mechanisms: stimulation with interferon (IFN)-γ or inhibition of methylation by treatment with 5-aza-2’-deoxycytidine (5-aza-dC). The effect of IFN-γ and 5-aza-dC on HLA expression was dependent on the cancer cell lines studied. However, in general, surface expression of HLA class Ia was induced on all cell lines. Surface expression of HLA-G was inconclusive but induction of HLA-G mRNA was prevalent upon treatment with 5-aza-dC and a combination of IFN-γ and 5-aza-dC. IFN-γ alone failed to induce HLA-G expression in the HLA-G-negative cell lines. The results support that HLA-G expression is regulated partly by DNA methylation. Furthermore, IFN-γ may play a role in the maintenance of HLA-G expression rather than inducing expression. The study demonstrates the feasibility of manipulating HLA expression and contributes to the exploration of mechanisms that can be potential targets for immunotherapy in breast cancer and malignant melanoma.

摘要

人类白细胞抗原 (HLA)-G作为新型癌症免疫治疗药物靶点的潜在作用增加了对HLA-G表达调控机制分析的兴趣,以及如何操纵表达式。我们表征了乳腺癌和恶性黑色素瘤细胞系中HLA的表达,并通过两种不同的机制研究了HLA-G表达的诱导: 干扰素 (IFN) 刺激-Γ 或通过 5-氮杂-2 '-脱氧胞苷 (5-aza-dC) 处理抑制甲基化。IFN-γ 和 5-aza-dC对HLA表达的影响依赖于所研究的癌细胞系。然而,一般来说,HLA Ia类的表面表达在所有细胞系上都被诱导。HLA-G的表面表达尚无定论,但在用 5-aza-dC和IFN-γ 和 5-aza-dC联合治疗时,HLA-G mRNA的诱导普遍存在。IFN-γ 单独诱导HLA-G阴性细胞系HLA-G表达失败。结果支持HLA-G表达部分受DNA甲基化调控。此外,IFN-γ 可能在HLA-G表达的维持中发挥作用,而不是诱导表达。该研究证明了操纵HLA表达的可行性,并有助于探索可作为乳腺癌和恶性黑色素瘤免疫治疗潜在靶点的机制。

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