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

Molecules. 2018 Aug 18;23(8):2071. doi: 10.3390/molecules23082071.


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.

Keywords: (−)-epigallocatechin gallate; epidermal growth factor; immune checkpoint; interferon-γ; lung tumor.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Catechin / chemistry
  • Catechin / pharmacology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Immunomodulation / drug effects*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tea / chemistry*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Phytogenic
  • B7-H1 Antigen
  • CD274 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tea
  • Catechin
  • Proto-Oncogene Proteins c-akt