Expression of PD-L1 Is Increased by Methionine Restriction Using Recombinant Methioninase in Human Colorectal Cancer Cells.

IF 2.6 4区 医学 Q2 GENETICS & HEREDITY
Kohei Mizuta, Byung Mo Kang, Qinghong Han, Yutaro Kubota, Sei Morinaga, Motokazu Sato, Michael Bouvet, Yasunori Tome, Kotaro Nishida, Robert M Hoffman
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Abstract

Background/aim: It has been recently demonstrated that a methionine-restricted diet increases the response to immune checkpoint inhibitors (ICIs) via an increase in PD-L1 in a syngeneic mouse colorectal-cancer model. Our laboratory has developed recombinant methioninase (rMETase) to restrict methionine. The aim of the present study was to determine if rMETase can increase PD-L1 expression in a human colorectal cancer cell line in vitro.

Materials and methods: We evaluated the half-maximal inhibitory concentration (IC50) value of rMETase on HCT-116 human colorectal cancer cells. HCT-116 cells were treated with rMETase at the IC50 Western immunoblotting was used to compare PD-L1 expression in HCT-116 cells treated with and without rMETase.

Results: The IC50 value of rMETase on HCT-116 was 0.79 U/ml. Methionine restriction using rMETase increased PD-L1 expression compared to the untreated control (p<0.05).

Conclusion: Methionine restriction with rMETase up-regulates PD-L1 expression in human colorectal cancer cells and the combination of rMETase and ICIs may have the potential to improve immunotherapy in human colorectal cancer.

在人类结直肠癌细胞中使用重组蛋氨酸酶限制蛋氨酸可增加 PD-L1 的表达。
背景/目的:最近有研究表明,在合成小鼠结直肠癌模型中,限制蛋氨酸饮食可通过增加 PD-L1 增加对免疫检查点抑制剂(ICIs)的反应。我们实验室开发了重组蛋氨酸酶(rMETase)来限制蛋氨酸。本研究旨在确定 rMETase 是否能在体外增加人结直肠癌细胞系中 PD-L1 的表达:我们评估了 rMETase 对 HCT-116 人类结直肠癌细胞的半数最大抑制浓度(IC50)值。用IC50值的rMETase处理HCT-116细胞,采用免疫印迹法比较用rMETase和不用rMETase处理的HCT-116细胞中PD-L1的表达:结果:rMETase对HCT-116细胞的IC50值为0.79 U/ml。与未经处理的对照组相比,使用 rMETase 限制蛋氨酸可增加 PD-L1 的表达(pConclusion):使用 rMETase 限制蛋氨酸可上调人类结直肠癌细胞中 PD-L1 的表达,rMETase 和 ICIs 的结合可能会改善人类结直肠癌的免疫疗法。
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来源期刊
Cancer Genomics & Proteomics
Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY
CiteScore
5.00
自引率
8.00%
发文量
51
期刊介绍: Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.
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