ArticleNature communications2021
Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 65 citations in OpenAlex.
- A Randomized Phase II Study of Combination Atezolizumab and Varlilumab (CDX-1127) with or without Cobimetinib in Previously Treated Unresectable Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- The role of miR-3917/HLA-DRB1 in Th17 cell differentiation affects chronic periodontitis.Odontology · 2026Article
- Upregulation of macrophage UPP1 promotes lung adenocarcinoma metastasis through an mtROS-cGAS-NLRP3 inflammasome axis.Cell death discovery · 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
- Regulatory role of IL-17-mediated inflammatory pathways in lung cancer initiation and progression.Discover oncology · 2026Review
- Deciphering Candida's Genomic Influence on Oral Squamous Cell Carcinoma: A Bioinformatics Approach.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Elevated IL-17A level is associated with poor overall survival following immune checkpoint inhibitors combined with targeted therapy in hepatocellular carcinoma with hyperbilirubinemia.Frontiers in immunology · 2026Article
- Th17-like cells and immunosuppressive macrophages infiltrate tertiary lymphoid structures with distinct maturation status in soft-tissue sarcoma.Cell death & disease · 2025Article
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer.Molecular cancer · 2025Article
- IL-17 triggers PD-L1 gene transcription in NSCLC cells via TRIM31-dependent MEF2C K63-linked polyubiquitination.BMC cancer · 2025Article
- Unveiling the nexus of p53 and PD-L1: insights into immunotherapy resistance mechanisms in hepatocellular carcinoma.American journal of cancer research · 2025Review
- Rewiring immune suppression in NSCLC: Roles and plasticity of Tregs and Th17 cells.Frontiers in immunology · 2025Review
- P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.Current medicinal chemistry · 2025Review
- CAF-induced physical constraints controlling T cell state and localization in solid tumours.Nature reviews. Cancer · 2024Review
- The role of IL-22 in cancer.Medical oncology (Northwood, London, England) · 2024Review
- Research into overcoming drug resistance in lung cancer treatment using CRISPR-Cas9 technology: a narrative review.Translational lung cancer research · 2024Review
- PIKfyve controls dendritic cell function and tumor immunity.bioRxiv : the preprint server for biology · 2024Article
- PIKfyve, expressed by CD11c-positive cells, controls tumor immunity.Nature communications · 2024Article
- RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Understanding resistance mechanisms to targeted therapies and immune checkpoint blockade in mutant KRAS lung cancers is critical to developing novel combination therapies and improving patient survival. Here, we show that MEK inhibition enhanced PD-L1 expression while PD-L1 blockade upregulated MAPK signaling in mutant KRAS lung tumors. Combined MEK inhibition with anti-PD-L1 synergistically reduced lung tumor growth and metastasis, but tumors eventually developed resistance to sustained combinatorial therapy. Multi-platform profiling revealed that resistant lung tumors have increased infiltration of Th17 cells, which secrete IL-17 and IL-22 cytokines to promote lung cancer cell invasiveness and MEK inhibitor resistance. Antibody depletion of IL-17A in combination with MEK inhibition and PD-L1 blockade markedly reduced therapy-resistance in vivo. Clinically, increased expression of Th17-associated genes in patients treated with PD-1 blockade predicted poorer overall survival and response in melanoma and predicated poorer response to anti-PD1 in NSCLC patients. Here we show a triple combinatorial therapeutic strategy to overcome resistance to combined MEK inhibitor and PD-L1 blockade.
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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 OpenQuestion graph.