CXCR1+ neutrophil infiltration orchestrates response to third-generation EGFR-TKI in EGFR mutant non-small-cell lung cancer

Although third-generation Epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKI) is standard of care for patients with EGFR-mutant Non-small cell lung cancer (NSCLC), little is known about the predictors of response or resistance. Here, we integrated single-cell RNA (scRNA) sequencin...

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Bibliographic Details
Published in:Signal transduction and targeted therapy 2024-12, Vol.9 (1), p.342-15
Main Authors: Wang, Haowei, Xiong, Anwen, Chen, Xiaoxia, Guo, Junhong, Tang, Zhuoran, Wu, Chunyan, Ren, Shengxiang, Zhou, Caicun, Chen, Jian, Hou, Likun, Jiang, Tao
Format: Article
Language:English
Subjects:
631/67/1612
631/67/1857
631/67/327
Animals
Cancer Research
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - immunology
Carcinoma, Non-Small-Cell Lung - pathology
Cell Biology
Cell Line, Tumor
Cell survival
Drug Resistance, Neoplasm - genetics
Epidermal growth factor receptors
ErbB Receptors - genetics
Female
Flow cytometry
Humans
Immunofluorescence
Infiltration
Internal Medicine
Leukocytes (neutrophilic)
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lung Neoplasms - pathology
Male
Medicine
Medicine & Public Health
Metastases
Mice
Mutants
Mutation
Neutrophil Infiltration - drug effects
Neutrophil Infiltration - genetics
Neutrophils
Neutrophils - immunology
NF-κB protein
Non-small cell lung carcinoma
Oncology
Pathology
Protein Kinase Inhibitors - pharmacology
Receptors, Interleukin-8A - genetics
Ribonucleic acid
RNA
Signal transduction
Small cell lung carcinoma
Tumor cells
Tumor necrosis factor-α
Tumors
Tyrosine kinase inhibitors
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Description
Summary:Although third-generation Epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKI) is standard of care for patients with EGFR-mutant Non-small cell lung cancer (NSCLC), little is known about the predictors of response or resistance. Here, we integrated single-cell RNA (scRNA) sequencing, bulk RNA sequencing, multiplexed immunofluorescence and flow cytometry data from pretreatment and post-resistant tumor samples of EGFR-mutant NSCLC patients received third-generation EGFR-TKIs. We show that resistant samples had a markedly enriched CXCR1 + neutrophils infiltration ( P  
ISSN:2095-9907
2059-3635
DOI:10.1038/s41392-024-02045-2