Evidence map›Paper›PMID 39090096›Full record

ArticleCell death & disease2024

PD-L1 induces autophagy and primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma via the MAPK signaling pathway.

Na Li, Ran Zuo, Yuchao He, Wenchen Gong, Yu Wang, Liwei Chen, Yi Luo, Cuicui Zhang, Zhiyong Liu, Peng Chen and 1 more

Abstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

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  17. Molecular and clonal evolution of primary lesionsTranslational lung cancer research · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Na Li *Department of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.ORCID 0000-0001-7005-3237
Ran Zuo *National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.ORCID 0009-0003-0483-6737
Yuchao He *National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.ORCID 0000-0001-5264-3700
Wenchen GongNational Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Yu WangNational Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Liwei ChenNational Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Yi LuoNational Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Cuicui ZhangDepartment of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Zhiyong LiuNational Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. liuzhiyong@tjmuch.com.ORCID 0000-0002-9964-7570
Peng ChenDepartment of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. chenpeng@tjmuch.com.ORCID 0009-0007-2417-5824
Hua GuoNational Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. guohua@tjmuch.com.ORCID 0000-0002-3345-8005

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82173208,82103672
6 · The paper itself

Abstract

Resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure and cancer recurrence in non-small cell lung cancer (NSCLC). Approximately 30% of patients with EGFR-activating mutations exhibit primary resistance to EGFR-TKIs. However, the potential mechanisms of primary resistance to EGFR-TKIs remain poorly understood. Recent studies have shown that increased expression of programmed death ligand-1 (PD-L1) is associated with EGFR-TKIs resistance. Therefore, the present study aimed to investigate the mechanism of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma (LUAD) cells. We found that PD-L1 was associated with poor prognosis in patients with EGFR-mutant LUAD, while the combination of EGFR-TKIs with chemotherapy could improve its therapeutic efficacy. In vitro and in vivo experiments revealed that PD-L1 promoted the proliferation and autophagy and inhibited the apoptosis of LUAD cells. Mechanistic studies demonstrated that upregulation of PD-L1 was critical in inducing autophagy through the mitogen-activated protein kinase (MAPK) signaling pathway, which was beneficial for tumor progression and the development of gefitinib resistance. Furthermore, we found that gefitinib combined with pemetrexed could synergistically enhance antitumor efficacy in PD-L1-overexpression LUAD cells. Overall, our study demonstrated that PD-L1 contributed to primary resistance to EGFR-TKIs in EGFR-mutant LUAD cells, which may be mediated by inducing autophagy via the MAPK signaling pathway. These findings not only help improve the prognosis of patients with EGFR-mutant LUAD but also provide a reference for the research of other cancer types.

Indexed as

Adenocarcinoma of LungAutophagyB7-H1 AntigenDrug Resistance, NeoplasmErbB ReceptorsLung NeoplasmsMAP Kinase Signaling SystemMutationProtein Kinase InhibitorsAnimalsApoptosisCell Line, TumorCell ProliferationFemaleGefitinibHumansB7-H1 AntigenCD274 protein, humanEGFR protein, humanErbB ReceptorsGefitinibProtein Kinase Inhibitors

Identifiers

PMID39090096
PMCPMC11294607

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.