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Molecules 2018, 23(8), 2071; https://doi.org/10.3390/molecules23082071

Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth

1
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
2
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan
3
Molecular Chirality Research Center and Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan
4
Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360-0197, Japan
5
Faculty of Medicine, Saga University, Saga 849-8501, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Hideyuki Ito
Received: 20 July 2018 / Revised: 15 August 2018 / Accepted: 16 August 2018 / Published: 18 August 2018
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Abstract

The anticancer activity of immune checkpoint inhibitors is attracting attention in various clinical sites. Since green tea catechin has cancer-preventive activity in humans, whether green tea catechin supports the role of immune checkpoint inhibitors was studied. We here report that (−)-epigallocatechin gallate (EGCG) inhibited programmed cell death ligand 1 (PD-L1) expression in non–small-cell lung cancer cells, induced by both interferon (IFN)-γ and epidermal growth factor (EGF). The mRNA and protein levels of IFN-γ–induced PD-L1 were reduced 40–80% after pretreatment with EGCG and green tea extract (GTE) in A549 cells, via inhibition of JAK2/STAT1 signaling. Similarly, EGF-induced PD-L1 expression was reduced about 37–50% in EGCG-pretreated Lu99 cells through inhibition of EGF receptor/Akt signaling. Furthermore, 0.3% GTE in drinking water reduced the average number of tumors per mouse from 4.1 ± 0.5 to 2.6 ± 0.4 and the percentage of PD-L1 positive cells from 9.6% to 2.9%, a decrease of 70%, in lung tumors of A/J mice given a single intraperitoneal injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In co-culture experiments using F10-OVA melanoma cells and tumor-specific CD3+ T cells, EGCG reduced PD-L1 mRNA expression about 30% in F10-OVA cells and restored interleukin-2 mRNA expression in tumor-specific CD3+ T cells. The results show that green tea catechin is an immune checkpoint inhibitor. View Full-Text
Keywords: (−)-epigallocatechin gallate; immune checkpoint; interferon-γ; epidermal growth factor; lung tumor (−)-epigallocatechin gallate; immune checkpoint; interferon-γ; epidermal growth factor; lung tumor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rawangkan, A.; Wongsirisin, P.; Namiki, K.; Iida, K.; Kobayashi, Y.; Shimizu, Y.; Fujiki, H.; Suganuma, M. Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth. Molecules 2018, 23, 2071.

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