To investigate the potential mechanisms underlying neutrophil extracellular traps (NETs) confer ferroptosis resistance and CD8(+) T cell inhibition in lung adenocarcinoma (LUAD). By the intravenous injection of LLC cells into the tail vein, a LUAD mouse model was created. Phorbol‐12‐myristate‐13‐acetate (PMA) stimulated neutrophils to facilitate NETs formation and combined with NETs inhibitor DNase I to explore NETs mechanism on LLC cell proliferation, migration, ferroptosis resistance, and CD8(+) T cell activity. CitH3, myeloperoxidase (MPO), cell‐free DNA, and MPO‐DNA levels in LUAD were increased, indicating an increase in NETs formation in LUAD. PMA promoted NETs formation in tumours of mice, increased the number of CD3(+)CD4(+) T cells, decreased perforin, granzyme A, granzyme B, IFNγ, and TNF‐α levels, and promoted LUAD growth and the number of lung tumour nodules, indicating that PMA promoted NETs formation, reduced the activity of CD8(+)T cells, and promoted LUAD growth. DNase I partially reversed the effects of PMA. NETs promoted LLC cell proliferation and migration, while DNase I reversed NETs effects. Erastin inhibited LLC cell proliferation and migration and promoted ferroptosis. NETs partially reversed Erastin effects. Further results showed that NETs promoted LLC cell proliferation and migration and inhibited ferroptosis by promoting YTHDF2‐mediated SLC2A3 mRNA degradation. Sh‐YTHDF2 partially reversed the effect of NETs on LLC cells, whereas si‐SLC2A3 partially reversed sh‐YTHDF2 effects on LLC cells. In addition, NETs inhibited LLC cell ferroptosis by inhibiting CD8(+) T cell activity. Sh‐YTHDF2 and DNase I inhibited NETs formation in tumours, increased the activity of CD8(+) T cells and inhibited LUAD growth. Our results suggested that NETs promoted the growth of LUAD through inhibiting ferroptosis and CD8(+) T cell activity by promoting YTHDF2‐mediated SLC2A3 mRNA degradation.

Background: Enhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD. Methods: First, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman’s correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumor tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer. Results: As a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway, Ras signaling pathway, etc. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumors, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumor types. Conclusion: Collectively, our results indicated that TBX5-AS1 may be a potential prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.

Background: Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non‐small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh‐endostatin), an antiangiogenic drug, and camrelizumab, an anti‐PD‐1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh‐endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC.Methods: Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh‐endostatin (70 mg/day, days 1–3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression‐free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles.Results: Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow‐up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23–13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment‐related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed.Conclusion: Rh‐endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients.