PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy

Chen, Kaiyan; Cheng, Guoping; Zhang, Fanrong; Zhu, Guanxia; Xu, Yanjun; Yu, Xiaoqing; Huang, Zhiyu; Fan, Yun

doi:10.1016/j.lungcan.2020.02.010

Cited by 61 publications

(58 citation statements)

References 36 publications

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“…The expression of PD-L1 was induced by EGFR and JAK2/STAT1, while the inhibition of JAK2 repressed the upregulation of PD-L1 in tumor cells and enhanced their immunogenicity ( Concha-Benavente et al, 2016 ). A clinical study showed that patients with EGFR mutation had increased PD-L1 expression and T cell infiltration ( Chen et al, 2020 ). The activation of STAT resulted in upregulated PD-L1 expression and the progression of lymphoma ( Estrada et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

2021

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Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.

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Section: Discussionmentioning

confidence: 99%

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

2021

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“…Some evidences indicate that suppression of the EGFR pathway via the reduction of eIF2α phosphorylation increases susceptibility to cellular oxidative stress [ 35 ]. It was also revealed in a clinical study that patients with EGFR mutation had increased PD-L1 expression and T cell infiltration [ 36 ]. The other identified core target, MAPK1, was responsible for the proliferation and survival of epithelial cells [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic targets and signaling mechanisms of vitamin C activity against sepsis: a bioinformatics study

Li¹,

Guo²,

Yu³

et al. 2020

Briefings in Bioinformatics

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Sepsis is a life-threatening complication of pneumonia, including coronavirus disease-2019 (COVID-19)-induced pneumonia. Evidence of the benefits of vitamin C (VC) for the treatment of sepsis is accumulating. However, data revealing the targets and molecular mechanisms of VC action against sepsis are limited. In this report, a bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets, biological functions, and the signaling pathways of VC action against sepsis. As shown in network assays, 63 primary causal targets for the VC action against sepsis were identified from the data, and four optimal core targets for the VC action against sepsis were identified. These core targets were epidermal growth factor receptor (EGFR), mitogen-activated protein kinase-1 (MAPK1), proto-oncogene c (JUN), and signal transducer and activator of transcription-3 (STAT3). In addition, all biological processes (including a top 20) and signaling pathways (including a top 20) potentially involved in the VC action against sepsis were identified. The hub genes potentially involved in the VC action against sepsis and interlaced networks from the Kyoto Encyclopedia of Genes and Genomes Mapper assays were highlighted. Considering all the bioinformatic findings, we conclude that VC antisepsis effects are mechanistically and pharmacologically implicated with suppression of immune dysfunction-related and inflammation-associated functional processes and other signaling pathways. These primary predictive biotargets may potentially be used to treat sepsis in future clinical practice.

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“…Nevertheless, some studies showed that patients with uncommon EGFR (including G719X, L861Q, S768I, and Ex20 ins) mutations have a good immunotherapy potential [15][16][17]. Because these EGFR mutations showed higher rates of concomitant PD-L1 expression and CD8 + TILs within the tumor microenvironment than the proportion in patients with classic sensitive mutations [7]. Therefore, immunotherapy for patients with rare EGFR mutations and its mechanism research are interesting direction.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, it has been reported that the high expression of PD-L1 was a factor of primary EGFR-TKI resistance [5,6]. In present, some studies have shown that different EGFR subtypes responded differently to immunotherapy, some rare EGFR mutations have immunotherapy potential [7][8][9]. Therefore, after exhaustion of targeted agents or naïve advanced EGFR-mutant with PD-L1 high expression, immunotherapy may be considered as a salvage treatment.…”

Section: Introductionmentioning

confidence: 99%

A Rare EGFR R748T Mutation in A Squamous Cell Lung Carcinoma Patient with PD-L1 High Expression and Response to Immuno-Chemo Combination Therapy

Sun

Lei

Liu

2020

Preprint

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Background: In present, patients with stage IV or recurrent/metastatic non-small cell lung cancer (NSCLC) whose tumors harbor programmed death ligand 1 (PD-L1) expression and active Epidermal Growth Factor Receptor (EGFR) mutations should receive initial EGFR tyrosine kinase inhibitors (TKIs) based on clinical guidelines and practice. However, high PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment advanced EGFR-mutant lung cancer patients, the optimal use of ICI therapy in patients with actionable EGFR mutations remains an important field of ongoing research. Some studies also showed that patients with uncommon EGFR mutations have a good immunotherapy potential.Case prestation: Here, we report a 56-year old advanced squamous cell lung carcinoma (SCC) patient with a rare active mutation in EGFR gene (EGFR p.R748T) and PD-L1 expression who responded well to the immune-chemo combination therapy (pembrolizumab with nab-paclitaxel and nedaplatin). Conclusion: The EGFR R748T mutation is an uncommon active mutation and there is no report about immuno-chemo therapy on patient with EGFR R748T mutation and PD-L1 high expression. The result presented in this case provides a feasible therapy for some patients who harbor rare active EGFR mutations (except for G719X, L861Q, S768I, and Ex20 ins) with high PD-L1 expression.

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PD-L1 expression and T cells infiltration in patients with uncommon EGFR-mutant non-small cell lung cancer and the response to immunotherapy

Cited by 61 publications

References 36 publications

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

Therapeutic targets and signaling mechanisms of vitamin C activity against sepsis: a bioinformatics study

A Rare EGFR R748T Mutation in A Squamous Cell Lung Carcinoma Patient with PD-L1 High Expression and Response to Immuno-Chemo Combination Therapy

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