ArticleCancer research2016
IL6 Blockade Reprograms the Lung Tumor Microenvironment to Limit the Development and Progression of K-ras-Mutant Lung Cancer.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
151 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- Research trends in lung cancer and the tumor microenvironment: a bibliometric analysis of studies published from 2014 to 2023.Frontiers in oncology · 2024Pooled it
- Influence of postoperative complications on long-term outcome after oncologic lung resection surgery. Substudy of a randomized control trial.Journal of clinical monitoring and computing · 2021Trial
- Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules.Molecules (Basel, Switzerland) · 2019Trial
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
- RAS signaling at the crossroads of radioresistance and tumor immunity.Journal for immunotherapy of cancer · 2026Review
- KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.Molecular cancer · 2026Review
- Chronic IL-21 exposure reshapes pulmonary environment, elevating risk of respiratory diseases.Cellular and molecular life sciences : CMLS · 2026Article
- Repurposing of the Macrolide Antibiotic Clarithromycin for the Prevention of Lung Cancer.Molecular cancer therapeutics · 2026Article
- RAS(ON) Multiselective Inhibition Drives Antitumor Immunity in Preclinical Models of NRAS-Mutant Melanoma.Cancer immunology research · 2026Article
- Fibroblast transformation in the tumor microenvironment of lung adenocarcinoma: heterogeneity, regulation, and therapeutic targeting.Frontiers in immunology · 2026Review
- DC subsets and states unraveled across human juxtatumoral and malignant tissues.Nature immunology · 2026Article
- [Research Progress on the Regulatory Mechanism of Respiratory Microbiota in the Comorbidity of Chronic Obstructive Pulmonary Disease and Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- COVID-19 and Lung Cancer Interactions: A Literature Review.Medical sciences (Basel, Switzerland) · 2025Review
- Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming.Cell death & disease · 2025Review
- [Research Progress on Interleukin-6 in Screening and Prognosis of Patients with Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy.Cytokine & growth factor reviews · 2025Review
- Exploring the metabolomics and metagenomics of chronic obstructive pulmonary disease (COPD) and lung cancer: unraveling the complex interplay.Journal of thoracic disease · 2025Review
- Shaping the battlefield: EGFR and KRAS tumor mutations' role on the immune microenvironment and immunotherapy responses in lung cancer.Cancer metastasis reviews · 2025Review
- Epigenetic silencing of DNA sensing pathway by FOXM1 blocks stress ligand-dependent antitumor immunity and immune memory.Nature communications · 2025Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors.
Funding
Abstract
Activating mutations of K-ras are the most common oncogenic alterations found in lung cancer. Unfortunately, attempts to target K-ras-mutant lung tumors have thus far failed, clearly indicating the need for new approaches in patients with this molecular profile. We have previously shown NF-κB activation, release of IL6, and activation of its responsive transcription factor STAT3 in K-ras-mutant lung tumors, which was further amplified by the tumor-enhancing effect of chronic obstructive pulmonary disease (COPD)-type airway inflammation. These findings suggest an essential role for this inflammatory pathway in K-ras-mutant lung tumorigenesis and its enhancement by COPD. Therefore, here we blocked IL6 using a monoclonal anti-IL6 antibody in a K-ras-mutant mouse model of lung cancer in the absence or presence of COPD-type airway inflammation. IL6 blockade significantly inhibited lung cancer promotion, tumor cell-intrinsic STAT3 activation, tumor cell proliferation, and angiogenesis markers. Moreover, IL6 inhibition reduced expression of protumor type 2 molecules (arginase 1, Fizz 1, Mgl, and IDO), number of M2-type macrophages and granulocytic myeloid-derived suppressor cells, and protumor T-regulatory/Th17 cell responses. This was accompanied by increased expression of antitumor type 1 molecule (Nos2), and antitumor Th1/CD8 T-cell responses. Our study demonstrates that IL6 blockade not only has direct intrinsic inhibitory effect on tumor cells, but also reeducates the lung microenvironment toward an antitumor phenotype by altering the relative proportion between protumor and antitumor immune cells. This information introduces IL6 as a potential druggable target for prevention and treatment of K-ras-mutant lung tumors. Cancer Res; 76(11); 3189-99. ©2016 AACR.
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