ArticleCancer research2024
Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non-Small Cell Lung Cancer.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advancing immune checkpoint inhibitor rechallenge: key insights into efficacy, safety, and personalized strategies in advanced solid tumors.Frontiers in oncology · 2026Pooled it
- Advancing the understanding of the immune escape in lung cancer immunotherapy: Global trends, collaborations, and future directions.Human vaccines & immunotherapeutics · 2026Article
- Targeting Wild-type NTRK in NTRK Fusion-Negative Lung Cancer Decreases Brain Metastases.Cancer research communications · 2026Article
- Tumor-Associated Platelets Suppress T-cell Function and Promote Immune Evasion in TNBC via the P-selectin/P-selectin Glycoprotein Ligand 1 Pathway.Cancer research communications · 2026Article
- Minimal residual disease assessment through ctDNA facilitates tailored immunotherapy in MSI-high, NTRK1-fusion pancreatic adenocarcinoma.The oncologist · 2026Article
- Disrupted renal clock and blood pressure rhythms in type 2 diabetic nephropathy.Clinical science (London, England : 1979) · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Immune checkpoint inhibitor-based combinatory and alternative strategies for immune treatment of lung cancers.Frontiers in immunology · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Development and validation of a circulating tumor DNA-based machine learning model for predicting immunotherapy response in non-small cell lung cancer.Translational cancer research · 2025Article
- Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects.Genes · 2025Review
- Unveiling the research directions for pyrrolidine-based small molecules as versatile antidiabetic and anticancer agents.Future medicinal chemistry · 2025Review
- Tumor-Associated Macrophages: Key Players in the Non-Small Cell Lung Cancer Tumor Microenvironment.Cancer medicine · 2025Review
- Igniting Cold Tumors: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance.Oncology research · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Treatment of non-small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anticancer effects of immune checkpoint inhibitors (ICI). However, only 20% of the patients with NSCLC benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 patients with NSCLC who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss-of-function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS when compared with patients with wild-type NTRK1. Notably, suppression of the NTRK1 pathway by knockdown or entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models. Comprehensive T-cell population analyses demonstrated that stem-like CD4+ T cells and effector CD4+ and CD8+ T cells were highly enriched in anti-PD-1-treated mice bearing tumors with decreased NTRK1 signaling. RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating cross-talk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcome immunotherapy resistance in patients with NSCLC with NTRK1 wild-type. Significance: Inhibition of NTRK1 signaling confers sensitivity to immunotherapy by enhancing complement C3-mediated T-cell and macrophage functions, leading to improved responses to immune checkpoint inhibitors in patients with lung cancer with NTRK1 mutations.
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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.