Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

Wang, Kaiyuan; Wang, Jian; Wei, Feng; Zhao, Ning; Yang, Fan; Ren, Xiubao

doi:10.3389/fimmu.2017.00456

Cited by 57 publications

(50 citation statements)

References 56 publications

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“…Consistent with this finding, there is a positive correlation between TLR4 and PD‐L1 expression in tumors . In addition, elevated TLR4 expression is associated with poor survival of cancer patients . Thus, DAMP‐mediated upregulation of PD‐L1 expression could contribute to the downregulation of immune activity during radiotherapy and DNA damage‐dependent chemotherapy.…”

Section: An Immune Response Mediated By Cell Death Signal After Dna Dsupporting

confidence: 61%

“…While DAMPs stimulate immune activity, leading to further cancer cell‐killing, HMGB1‐mediated TLR4/MyD88/TRIF signaling upregulates PD‐L1 expression in surrounding viable cancer cells . Consistent with this finding, there is a positive correlation between TLR4 and PD‐L1 expression in tumors . In addition, elevated TLR4 expression is associated with poor survival of cancer patients .…”

Section: An Immune Response Mediated By Cell Death Signal After Dna Dmentioning

confidence: 53%

“…36 Consistent with this finding, there is a positive correlation between TLR4 and PD-L1 expression in tumors. 37 In addition, elevated TLR4 expression is associated with poor survival of cancer patients. 37 show better therapeutic outcomes after radiotherapy that might promote the release of DAMPs subsequent to radiotherapy.…”

Section: An Immune Re S P On S E Med Iated By Cell De Ath S I G Nalmentioning

confidence: 99%

“…37 In addition, elevated TLR4 expression is associated with poor survival of cancer patients. 37 show better therapeutic outcomes after radiotherapy that might promote the release of DAMPs subsequent to radiotherapy. 38 In contrast, it is well known that the activity of the HR pathway is downregulated in certain tumors.…”

Section: An Immune Re S P On S E Med Iated By Cell De Ath S I G Nalmentioning

confidence: 99%

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Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

2019

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Anti‐programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) therapy, which is one of the most promising cancer therapies, is licensed for treating various tumors. Programmed death‐ligand 1, which is expressed on the surface of cancer cells, leads to the inhibition of T lymphocyte activation and immune evasion if it binds to the receptor PD‐1 on CTLs. Anti‐PD‐1/PD‐L1 Abs inhibit interactions between PD‐1 and PD‐L1 to restore antitumor immunity. Although certain patients achieve effective responses to anti‐PD‐1/PD‐L1 therapy, the efficacy of treatment is highly variable. Clinical trials of anti‐PD‐1/PD‐L1 therapy combined with radiotherapy/chemotherapy are underway with suggestive evidence of favorable outcome; however, the molecular mechanism is largely unknown. Among several molecular targets that can influence the efficacy of anti‐PD‐1/PD‐L1 therapy, PD‐L1 expression in tumors is considered to be a critical biomarker because there is a positive correlation between the efficacy of combined treatment protocols and PD‐L1 expression levels. Therefore, understanding the mechanisms underlying the regulation of PD‐L1 expression in cancer cells, particularly the mechanism of PD‐L1 expression following DNA damage, is important. In this review, we consider recent findings on the regulation of PD‐L1 expression in response to DNA damage signaling in cancer cells.

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Section: An Immune Response Mediated By Cell Death Signal After Dna Dsupporting

confidence: 61%

Section: An Immune Response Mediated By Cell Death Signal After Dna Dmentioning

confidence: 53%

Section: An Immune Re S P On S E Med Iated By Cell De Ath S I G Nalmentioning

confidence: 99%

Section: An Immune Re S P On S E Med Iated By Cell De Ath S I G Nalmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

2019

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“…In this study, we established TLR4/MYD88/STAT3 and TLR4/TRIF/STAT3 pathways in melanoma and demonstrated their pathogenic roles. TLR4 expression and constitutive STAT3 activation are also found in other cancers, such as liver 52 , lung 53,54 , and stomach cancers 55 .…”

Section: Discussionmentioning

confidence: 98%

Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression

Liu

Wang

et al. 2020

Cell Death Dis

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Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial-mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.

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CXCR5 and TLR4 signals synergistically enhance non‐small cell lung cancer progression

Shin,

Kim,

Kim

et al. 2024

Clinical & Translational Med

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Dear Editor, Chemokines and their receptors play essential roles in neoplastic transformation, tumour cell growth and survival, and organ-specific metastasis during carcinogenesism. [1][2][3] Of various CXC chemokines, CXCL13 and its related receptor CXCR5 have been implicated in lung cancer progression. 2 However, the molecular and cellular mechanisms by which the CXCR5-CXCL13 signal axis is functionally regulated in lung cancer progression are still poorly understood. Through clinical microarray data analysis of primary non-small cell lung cancer (NSCLC; n = 42) patients, we found that the up-regulation of CXCR5 and CXCL13 or CXCR5 and TLR4 in lung tumour tissues versus matched lung normal tissues was significantly associated with gene sets related to cancer module, lung fibrosis, VEGF, chemokine, cytokine and TLR signalling pathway. Through functional analysis with CXCR5knockout (CXCR5-KO) human lung cancer cells generated by CRISPR/Cas9 gene editing method, we found that the CXCR5-CXCL13 axis was functionally linked to TLR4 signalling through activation of NF-κB for lung cancer progression, strongly suggesting that our clinically comparative results and functional investigations of TLR4-CXCR5 signalling network in lung cancer could potentially contribute to translational approaches for the development of lung cancer therapeutic agents.Gene expression profiling interactive analysis (http:// gepia.cancer-pku.cn/detail.php?gene = CXCR5) revealed a positive correlation between CXCR5 and CXCL13 expression in lung adenocarcinoma (LUAD) (Figure S1A; p = 3.8e−08, R = 0.25). The expression of CXCL13 was significantly enhanced in LUAD and lung squamous cell carcinoma (Figures S1B and C). To clinically get insight into the role of the CXCR5-CXCL13 axis, we utilised microarray data of primary NSCLC patients' lung tumour tissues (n = 42; Table S1) and their matched lung normal tissues (n = 42). We performed a gene Ji Hye Shin, Mi-Jeong Kim and Ji Young Kim contributed equally to this work.

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Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

Cited by 57 publications

References 56 publications

Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression

CXCR5 and TLR4 signals synergistically enhance non‐small cell lung cancer progression

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