ArticleNature communications2025
ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Exploration of the Potential Mechanisms of Yinqiao Powder in Treating Atopic Dermatitis: Integrating Network Pharmacology, Single-Cell, and Bulk RNA Sequencing.Journal of asthma and allergy · 2026Trial
- CREBBP loss drives immune evasion by epigenetically silencing STING and MHC-I in small cell lung cancer.Science advances · 2026Article
- Review
- NRGN inhibits CD8⁺ T cell effector function by downregulating MHC-I expression through the FMR1-IRF8 axis in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Distinct immune microenvironment in HER2-low triple-negative breast cancer underlies inferior response to immunotherapy.NPJ precision oncology · 2026Article
- Optimization of ultrasound-assisted extraction of Sargassum polycystum for antitumor activity: Multi-objective optimization and mechanistic insights.Ultrasonics sonochemistry · 2026Article
- Single-cell omics in tumor lymph node metastasis: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- Targeting lysine acetyltransferase 6A/B in cancer: a conceptual and translational review of epigenetic regulation, immune microenvironment remodeling, and the dual-compartment hypothesis.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
Small cell lung cancer (SCLC) is characterized by its highly aggressive phenotype and dismal outcome. Despite the benefit of adding immune checkpoint blockade to standard chemotherapy, tumors acquire the ability to evade immunosurveillance and develop resistance. To investigate these underlying mechanisms, we perform high-dimensional profiling of human and murine SCLC specimens. In matched primary and metastatic human samples, we observe MHC-I loss in metastases, highlighting its role in immune evasion. Correspondingly, silencing MHC-I in SCLC cells drastically reduces immune infiltration and promotes metastasis in mice. Using mass spectrometry and phospho-tyrosine kinase analyses, we identify ERBB2 signaling as a suppressor of MHC-I and driver of immune-modulatory transcripts. Mechanistically, genetic and pharmacologic blockade of ERBB2 induces MHC-I in a STING-dependent manner and prevents immune evasion in autochthonous murine SCLC. Strikingly, combining ERBB2 inhibition with anti-PD-1 elicits profound synergistic responses in preclinical models, suggesting this combination for future clinical trials in SCLC patients.
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Registered trials
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.