ArticleJournal of translational medicine2023
IL-17A promotes tumorigenesis and upregulates PD-L1 expression in non-small cell lung cancer.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 43 citations in OpenAlex.
- IL-17/IL-17RA Axis Facilitates Immune Evasion in Hepatocellular Carcinoma by Upregulating PD-L1 via the NF-κB Pathway.Digestive diseases and sciences · 2026Article
- TSC22D4 drives clear cell renal cell carcinoma progression and therapy resistance by stabilizing NRF2 through KEAP1 disruption.Cell death & disease · 2026Article
- Th17-mediated antitumor immunity in patient-derived organoid and autologous immune cell cocultures predicts response to immunotherapy in head and neck cancer.Immuno-oncology technology · 2026Article
- High Programmed Death-Ligand 1 Expression is Associated With a Shorter Progression Free Survival in ALK-Rearranged Lung Cancer Patients Treated With First Line Tyrosine Kinase Inhibitors.Clinical lung cancer · 2026Article
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- Enhanced Anti-Lung Cancer Efficacy of Neo-BCV Combined with Cisplatin: Immune Activation and Tumor Microenvironment Remodeling.Vaccines · 2026Article
- Regulatory role of IL-17-mediated inflammatory pathways in lung cancer initiation and progression.Discover oncology · 2026Review
- Multi-omics analysis and experimental validation uncovers prognosis significance of IKBIP in patients with hepatocellular carcinoma: a multicenter cohort study.BMC gastroenterology · 2026Article
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Review
- Interleukin-17 A and diabetic kidney disease: emerging evidence on its pathogenic role and targeted modulation.Acta diabetologica · 2026Review
- Bidirectional Mendelian randomization identifies differential causal associations between inflammatory cytokines and lung cancer subtypes.Discover oncology · 2026Article
- Machine learning-based signature for prognosis and drug sensitivity in hepatocellular carcinoma using glycolysis-related gene.Oncology letters · 2026Article
- Circulating cytokines as potential dynamic biomarkers of PD-1 blockade response and prognosis in non-small cell lung cancer.Frontiers in immunology · 2026Review
- The IL-1R and NFKBIZ pathway mediates immunoregulatory responses and immunotherapy efficacy in anaplastic large cell lymphoma.Leukemia · 2026Article
- Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis.Journal of translational autoimmunity · 2025Article
- Comprehensive pan-cancer analysis of p62 reveals its contribution to shaping tumor microenvironment and anti-tumor immunity.Discover oncology · 2025Article
- Targeting autophagy to enhance cancer immunotherapy: emerging mechanisms and strategies.Medical oncology (Northwood, London, England) · 2025Review
- Overlapping risk factors and pathogenic mechanisms in lung cancer and cardiovascular disease.Discover oncology · 2025Review
- Pathogenesis of Cutaneous Mycobacterial Infections-International journal of molecular sciences · 2025Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe tumor microenvironment plays a key role in non-small cell lung cancer (NSCLC) development and also influences the effective response to immunotherapy. The pro-inflammatory factor interleukin-17A mediates important immune responses in the tumor microenvironment. In this study, the potential role and mechanisms of IL-17A in NSCLC were investigated.
methodsWe detected IL-17A by immunohistochemistry (IHC) in 39 NSCLC patients. Its expression was correlated with the programmed cell death-ligand1 (PD-L1). IL-17A knockdown and overexpression in A549 and SPC-A-1 cell models were constructed. The function of IL-17A was examined in vitro by wound healing, migration, invasion, plate colony formation and T cell killing assay. Western blot analysis, immunofluorescence assay and IHC were performed to investigate the regulation effects of IL-17A on autophagy in A549 and SPC-A-1. The effect of IL-17A on ROS/Nrf2/p62 signaling pathway was detected. Subcutaneous tumor models were established to examine the tumor-promoting effect of IL-17A in vivo and its effect on immunotherapy.
resultsWe found a prevalent expression of IL-17A in NSCLC tumor tissues and it was positively correlated with PD-L1 expression (r = 0.6121, p < 0.0001). In vitro, IL-17A promotes lung cancer cell migration, invasion and colony formation ability. Moreover, IL-17A upregulated N-cadherin, Twist, and Snail, and downregulated E-cadherin in NSCLC cells. IL-17A enhanced cell survival in the T cell killing assay. Mechanistically, IL-17A induced ROS production and increased Nrf2 and p62 expression, thereby inhibiting autophagy and reducing PD-L1 degradation. In vivo experiments, anti-IL-17A monoclonal antibody alone slowed the growth of subcutaneous tumors in mice. When combined with anti-PD-L1 monoclonal antibody, tumor tissue expression of PD-L1 was reduced and the therapeutic effect was diminished.
conclusionWe found that IL-17A promoted NSCLC progression and inhibited autophagy through the ROS/Nrf2/p62 pathway leading to increased PD-L1 expression in cancer cells. Modulation of IL-17A may affect the therapeutic efficacy of immunotherapy.
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