MYC expression correlates with PD-L1 expression in non-small cell lung cancer

Kim, Eun Young; Kim, Arum; Kim, Se Kyu; Chang, Yoon Soo

doi:10.1016/j.lungcan.2017.06.006

Cited by 87 publications

(59 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent report showed that melanomas arising during pregnancy are associated with higher GPER protein within tumor sections, suggesting that hormonal factors may upregulate GPER expression (Fábián et al, 2017). Consistent with these clinical data, G-1 induced a dose-dependent increase in GPER expression in melanoma cells ( Beyond its role in stimulating proliferation and inhibiting differentiation, c-Myc was recently shown to contribute to tumor aggressiveness by promoting expression of multiple inhibitory immune checkpoint regulators on tumor cells including PD-L1 (Casey et al, 2016;Kim et al, 2017). Consistent with this, pharmacologic GPER activation in melanoma cells resulted in parallel decreases in both c-Myc and PD-L1 ( Figure 4A-C).…”

Section: Resultssupporting

confidence: 53%

“…c-Myc drives many cancers including melanoma, and despite intensive effort since its discovery nearly 40 years ago, efforts to inhibit c-Myc with systemically-tolerated agents have generally been unsuccessful, and there are still no FDA approved c-Myc inhibitors. High c-Myc protein in tumor cells inhibits expression of antigen presenting HLA/ MHC (Schlagbauer-Wadl et al, 1999) and activates expression of PD-L1 (Casey et al, 2016;Kim et al, 2017). These combined effects of c-Myc activation render tumors less visible to immune cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

1244 Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade

Natale

Zhang

et al. 2018

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Female sex and history of prior pregnancies are associated with favorable melanoma outcomes. Here, we show that much of the melanoma protective effect likely results from estrogen signaling through the G protein-coupled estrogen receptor (GPER) on melanocytes. Selective GPER activation in primary melanocytes and melanoma cells induced long-term changes that maintained a more differentiated cell state as defined by increased expression of well-established melanocyte differentiation antigens, increased pigment production, decreased proliferative capacity, and decreased expression of the oncodriver and stem cell marker c-Myc. GPER signaling also rendered melanoma cells more vulnerable to immunotherapy. Systemically delivered GPER agonist was well tolerated, and cooperated with immune checkpoint blockade in melanoma-bearing mice to dramatically extend survival, with up to half of mice clearing their tumor. Complete responses were associated with immune memory that protected against tumor rechallenge. GPER may be a useful, pharmacologically accessible target for melanoma.

show abstract

Section: Resultssupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

1244 Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade

Natale

Zhang

et al. 2018

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…Indeed, both loss-of-function (mutations or deletion) of tumor suppressor FBXW7 and overexpression of c-MYC oncoprotein correlate with PD-L1 expression levels and poor prognosis in some malignancies. 41,42 Therefore, whether anti-PD-L1/ PD-1 immunotherapy induces better effect in GBM patients with FBXW7 inactivation and/or MYC activation remains further investigation.…”

Section: Discussionmentioning

confidence: 99%

Neddylation inhibition upregulates PD‐L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma

Zhou

Zhao

Yang

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Pevonedistat (MLN4924), a specific NEDD8‐activating enzyme inhibitor, has been considered as a promising treatment for glioblastoma, which is currently in Phase I/II clinical trials. On the other hand, inhibition of neddylation pathway substantially upregulates the expression of T cell negative regulator programmed death‐ligand 1 (PD‐L1), which might account for the potential resistance via evasion of immune surveillance checkpoints. Whether administration of anti‐PD‐L1 enhances the efficacy of pevonedistat through a cytotoxic T cell‐dependent mechanism in glioblastoma needs to be investigated. Here, we report that depletion of neddylation pathway key enzymes markedly elevates PD‐L1 expression in glioblastoma cancer cells. Consistently, neddylation inhibitor pevonedistat significantly enhances PD‐L1 expression in both glioblastoma cancer cell lines and animal models. Mechanistically, pevonedistat increases PD‐L1 mRNA levels mainly through inhibiting Cullin1‐F‐box and WD repeat domain‐containing 7 E3 ligase activity and accumulating c‐MYC proteins, a direct transcriptional activator of PD‐L1 gene expression. In addition, inhibition of Cullin3 activity by pevonedistat also blocks PD‐L1 protein degradation. Importantly, pevonedistat attenuates T cell killing through PD‐L1 induction, and blockade of PD‐L1 restores the sensitivity of pevonedistat‐treated glioblastoma cancer cells to T cell killing. The combination of pevonedistat and anti‐PD‐L1 therapy compared to each agent alone significantly increased the therapeutic efficacy in vivo. Our study demonstrates inhibition of neddylation pathway suppresses cancer‐associated immunity and provides solid evidence to support the combination of pevonedistat and PD‐L1/programmed cell death protein 1 immune checkpoint blockade as a potential therapeutic strategy to treat glioblastoma.

show abstract

“…The high expression of LIFR (41) is an independent prognostic marker for primary melanoma (41,42). MYC regulation in the cervical cancer immune response has an irreplaceable role (43)(44)(45)(46)(47). The protein encoded by the CD46 gene is a type I membrane protein that is part of the complement system.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes in cervical cancer by bioinformatics analysis

Zhang

Xiao

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Cervical cancer is the most common gynecological malignancy. In recent years, the incidence of cervical cancer has had a younger trend. Cervical cancer morbidity and mortality rates have been significantly reduced due to recent decades of cervical cytology screening leading to the early detection and treatment of cervical cancer and precancerous lesions. There are a number of methods used to treat cervical cancer and improve the survival rate. However, the prevalence and recurrence rates of cervical cancer are increasing every year. There is an urgent requirement for a better understanding of the molecular mechanism cervical cancer development. The present study used scientific information retrieval from the Gene Expression Omnibus database to download the GSE26511 dataset, which contained 39 samples, including 19 cervical cancer lymph node-positive samples and 20 cervical cancer lymph node-negative samples. Using Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and weighted gene co-expression network analysis, 1,263 differentially expressed genes were found that affected the biological processes, including 'cell cycle process', 'signaling pathways', 'immune response', 'cell activation', 'regulation of immune system process' and 'inflammatory response'. These areas should be the focus of study for cervical cancer in the future.

show abstract

MYC expression correlates with PD-L1 expression in non-small cell lung cancer

Cited by 87 publications

References 18 publications

1244 Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade

1244 Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade

Neddylation inhibition upregulates PD‐L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma

Identification of differentially expressed genes in cervical cancer by bioinformatics analysis

Contact Info

Product

Resources

About