A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer

Tao, Lihua; Zhou, Xinru; Li, Fuchao; Chen, Qi; Meng, Fan‐Yi; Mao, Yong; Li, Rui; Hua, Dong; Zhang, Hongjian; Wang, Weipeng; Chen, Weichang

doi:10.1007/s00262-016-1936-0

Cited by 53 publications

(52 citation statements)

References 36 publications

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“…On the other hand, PD‐L1 is generally produced by cancer cells to escape immune surveillance, and is a molecular target for cancer immune therapy . Previous report showed that the PD‐L1 gene promoter is regulated by DNA methylation or Sp1 binding in cancer cells . There is the possibility that ATF7IP/MCAF1 may control PD‐L1 expression via Sp1,as indicated by published ChIP‐seq data of colon cancer (Figure A).…”

Section: Resultsmentioning

confidence: 89%

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Computational analysis of morphological and molecular features in gastric cancer tissues

et al. 2020

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Biological morphologies of cells and tissues represent their physiological and pathological conditions. The importance of quantitative assessment of morphological information has been highly recognized in clinical diagnosis and therapeutic strategies. In this study, we used a supervised machine learning algorithm wndchrm to classify hematoxylin and eosin (H&E)‐stained images of human gastric cancer tissues. This analysis distinguished between noncancer and cancer tissues with different histological grades. We then classified the H&E‐stained images by expression levels of cancer‐associated nuclear ATF7IP/MCAF1 and membranous PD‐L1 proteins using immunohistochemistry of serial sections. Interestingly, classes with low and high expressions of each protein exhibited significant morphological dissimilarity in H&E images. These results indicated that morphological features in cancer tissues are correlated with expression of specific cancer‐associated proteins, suggesting the usefulness of biomolecular‐based morphological classification.

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Section: Resultsmentioning

confidence: 89%

“…[41][42][43] Previous report showed that the PD-L1gene promoter is regulated by DNA methylation or Sp1 binding in cancer cells. 44,45 There is the possibility that ATF7IP/MCAF1 may control PD-L1 expression via Sp1,as indicated by published ChIP-seq data of colon cancer ( Figure S3A).…”

Section: Expression Levels Of Nuclear Atf7ip/ Mcaf1 Are Correlated mentioning

confidence: 99%

Computational analysis of morphological and molecular features in gastric cancer tissues

et al. 2020

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“…The single nucleotide polymorphism (SNP) rs4143815C>G in the 3 UTR of PD-L1 has been associated with an increased cancer risk and might be used as biomarker to predict the susceptibility to cancer [76]. Two polymorphisms characterized by >G changes localized in the 5 UTR of PD-L1 serve as binding site for SP1 [77] thereby affecting PD-L1 expression. Thus, variations in the PD-L1 promoter could lead to an overexpression.…”

Section: Pd-1 and Cd274 Polymorphismsmentioning

confidence: 99%

Basis of PD1/PD-L1 Therapies

Seliger

2019

JCM

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It is obvious that tumor cells have developed a number of strategies to escape immune surveillance including an altered expression of various immune checkpoints, such as the programmed death-1 receptor (PD-1) and its ligands PD-L1 and PD-L2. The interaction between PD-1 and PD-L1 results in an activation of self-tolerance pathways in both immune cells as well as tumor cells. Thus, these molecules represent excellent targets for T cell-based immunotherapies. However, the efficacy of therapies using checkpoint inhibitors is variable and only a limited number of patients receive a long-term response, while others develop resistances. Therefore, a better insight into the constitutive expression levels and their control as well as the predictive and prognostic value of PD-1/PD-L1, which are controversially discussed due to the methodological assessment, the dynamic and time-related variable expression of these molecules, is urgently required. In this review, the current knowledge of the PD-L1 and PD-1 genes, their expression in immune and tumor cells, the underlying molecular mechanisms of their regulation and their association with clinical parameters and therapy responses are summarized.

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“…12 PD-L1 is expressed in a variety of cancer cells, such as prostate cancer, lung cancer, and melanoma. 16,17 PD-L1 has also been a potential therapeutic target for gastric cancers. Reportedly, the expression of PD-L1 is upregulated and associated with a worse overall survival of gastric cancers.…”

Section: Introductionmentioning

confidence: 99%

“…Reportedly, the expression of PD-L1 is upregulated and associated with a worse overall survival of gastric cancers. 16,17 PD-L1 has also been a potential therapeutic target for gastric cancers. 18 However, how PD-L1 expression is upregulated in gastric cancers remains elusive.…”

Section: Introductionmentioning

confidence: 99%

LPS promotes the expression of PD‐L1 in gastric cancer cells through NF‐κB activation

Jun-quan

Zhu

et al. 2018

J of Cellular Biochemistry

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Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death-ligand 1 (PD-L1, B7-H1) is a member of the B7 family of cell surface ligands, which binds the PD-1 transmembrane receptor and inhibits T-cell activation within cancer tissues. It has been reported that the expression of PD-L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD-L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD-L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD-L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor-κB (NF-κB) activation was involved in PD-L1 expression in gastric cancer cells exposed to LPS stimulation through p65-binding to the PD-L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS-NF-κB-PD-L1 axis.

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A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer

Cited by 53 publications

References 36 publications

Computational analysis of morphological and molecular features in gastric cancer tissues

Computational analysis of morphological and molecular features in gastric cancer tissues

Basis of PD1/PD-L1 Therapies

LPS promotes the expression of PD‐L1 in gastric cancer cells through NF‐κB activation

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