PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation

Ji, Mei; Liu, Yan; Li, Qing; Li, Xiaodong; Zhao, Weiqing; Zhang, Hanze; Zhang, Xiaofei; Jiang, Jingting; Wu, Changping

doi:10.1186/s12967-014-0373-0

Cited by 69 publications

(42 citation statements)

References 70 publications

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“…Coincidentally, NSCLC patients with these clinicopathologic factors were inclined to have EGFR‐activating mutations. Consistently, high PD‐L1 expression was likely to be associated with the presence of EGFR‐activating mutations in NSCLC, and increased PD‐L1 expression can be considered an independently negative prognosis indicator for NSCLC . In our study, the cell surface expression of PD‐L1 was high in both the HCC827 sensitive cell line and the H1975 resistant cell line, both of which had an EGFR‐activating mutation (a E476‐A750 deletion mutation in exon 19 for the HCC827 cell line and a L858R point mutation in exon 21 for the H1975 cell line).…”

Section: Discussionsupporting

confidence: 76%

CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

Fu²,

Zhu³

et al. 2018

Molecular Carcinogenesis

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The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using 18F‐fluorodeoxyglucose (18F‐FDG) PET/CT imaging in non‐small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR‐TKI responses were used to detect p‐EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of 18F‐FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ‐radioimmunoassays in vitro and micro‐PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming. Correlation analyses were performed to investigate the association between CD147 expression and PD‐L1 expression in stable NSCLC cell lines. Higher CD147 expression was found in EGFR‐TKI‐sensitive NSCLC cell lines than in relatively resistant NSCLC cell lines (HCC827>PC9>A549>H1975). CD147 could promote 18F‐FDG uptake by HCC827 and H1975 cells in vitro and in vivo through an EGFR‐initiated Akt/mTOR‐dependent signaling pathway. Programmed cell death‐ligand 1 (PD‐L1) expression was positively correlated with CD147 expression in human NSCLC cell lines. EGFR‐TKI treatment sensitivity prediction in NSCLC using 18F‐FDG PET/CT imaging significantly correlated with CD147‐mediated glucose metabolic regulation via the Akt/mTOR‐dependent pathway. Moreover, PD‐L1 expression in NSCLC cell lines could be regulated by CD147, suggesting a potential immunosuppression induced by the upregulation of tumor glucose metabolism.

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Section: Discussionsupporting

confidence: 76%

CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

Fu²,

Zhu³

et al. 2018

Molecular Carcinogenesis

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“…45 ICI strategies have shown significant success in clinical studies of nonsmall-cell lung cancer, renal cell carcinoma, and melanoma, even though the responses are limited to 10-20%. 46,47 Several studies reported that the majority of intratumoral Tregs upregulate immune checkpoint molecules 17,[48][49][50] , making Tregs as a key target for ICI. Despite the clinical success to date, the exact mechanism of ICI is still elusive.…”

Section: Targeting Tregs For Cancer Immunotherapymentioning

confidence: 99%

Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells

2017

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Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME. Recent studies have shown that immune checkpoint molecules promote cancer progression through various antitumor inhibitory mechanisms. Recent advances in cancer immunotherapy have shown the promising potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune responses and clinical benefits in patients with cancer at late stages. Most studies revealed the effect of ICIs on T effector cells, and little is known about their effect on Tregs. In this review, we highlight the effects of the ICIs, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti-TIGIT, on tumor-infiltrating and peripheral Tregs to elicit effector T-cell functions against tumors. Additionally, we discuss how ICIs may target Tregs for cancer immunotherapy.

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“…48,49 A new class of drugs target PD-1 or PD-L1 and are reported to have activity against some malignancies including non-small cell lung cancers. 50,51 These drugs are useful for treatment of patients when standard chemotherapy has become ineffective. Nivolumab and pembrolizumab have been approved for treatment of non-small cell lung cancer, including both squamous cell carcinoma and adenocarcinoma.…”

Section: Committee IVmentioning

confidence: 99%

Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology

Layfield

Roy‐Chowdhuri

Baloch

et al. 2016

Diagnostic Cytopathology

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The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT-guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS-FNA), as well as recommendations for classification and criteria, ancillary testing and post-cytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next-generation sequencing are discussed.

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PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation

Cited by 69 publications

References 70 publications

CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells

Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology

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PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation

Cited by 69 publications

References 70 publications

CD147‐mediated glucose metabolic regulation contributes to the predictive role of 18F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

CD147‐mediated glucose metabolic regulation contributes to the predictive role of 18F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells

Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology

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CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC