ArticleNeuro-oncology2025
CAF-derived LRRC15 orchestrates macrophage polarization and limits PD-1 immunotherapy efficacy in glioblastoma.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Trends and hotspots in research related to tumor immune escape: bibliometric analysis and future perspectives.Frontiers in immunology · 2025Pooled it
- F7 Drives Gastric Cancer Metastasis Through Anoikis Resistance and Tumor Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tumor stroma-immune interactions shape the immunosuppressive microenvironment and predict response to neoadjuvant chemoradiotherapy plus immunotherapy in rectal cancer.Journal for immunotherapy of cancer · 2026Observational
- Tumor-Derived LAMB3 Drives Immunosuppressive LRRC15Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Molecular Structure, Expression, and Emerging Role of the 15-Leucine-Rich Repeat Containing Membrane Protein (LRRC15) in Skeletal Biology and Diseases.International journal of molecular sciences · 2026Review
- Anoikis in cancer: molecular mechanisms, resistance, and therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Single cell and spatial atlas of macrophage and astrocyte interactions in glioblastoma.Discover oncology · 2026Article
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Targeting LRRC15 in Cancer-Associated Fibroblasts Modifies the Extracellular Matrix and Enhances Tumor Immune Responses to Suppress Lung Cancer Progression.Cancer research · 2026Article
- Review
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- Spatiotemporal and metabolic heterogeneity of tumor-associated macrophages in glioblastoma: from single-cell insights to therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Pericyte-derived cancer-associated fibroblasts correlate with poor survival and are enriched after chemoradiotherapy in glioblastoma.PloS one · 2026Article
- Mapping the landscape: a comprehensive bibliometric analysis of immunotherapy advances in glioblastoma research.Discover oncology · 2025Article
- Spatial-reprogramming derived GPNMBGenome medicine · 2025Article
- Characteristics of the tumor microenvironment and potential immunotherapy strategies in renal cell carcinoma.Frontiers in immunology · 2025Review
- LRRC15+ Myofibroblasts as a Stromal State Linking Repair, Fibrosis, and Scarring.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair SocietyReview
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundThe effectiveness of PD-1/PD-L1 immune checkpoint blockade therapy in glioblastoma (GBM) is limited due to the tumor immunosuppressive microenvironment (TIME). Therefore, strategies of reprogramming TIME to a pro-inflammatory state offer a promising therapeutic approach.
methodsWe applied bioinformatics analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (stRNA-seq) to identify a significant accumulation of cancer-associated fibroblasts (CAFs) subclusters with elevated LRRC15 expression in the nonresponders to anti-PD-1 therapy. The molecular mechanism of LRRC15 was functionally validated in vitro and in vivo.
resultsThese CAFs subclusters drive the infiltration of macrophages (Mφ) into the tumor microenvironment and promote their polarization toward the M2 phenotype. Deletion of Lrrc15 in CAFs significantly restrained tumor growth and prolonged survival in mouse models. Mechanistically, LRRC15 in CAFs promotes IL8 expression by activating the downstream FAK/SRC/NF-κB pathways, leading to Mφ migration and M2-like polarization. In turn, M2-like Mφs secrete TGF-β, which induces LRRC15 expression in CAFs via SMAD2-dependent transcriptional activation. Targeting CAFs subcluster with elevated LRRC15 expression in combination with anti-PD-1 treatment enhanced antitumor efficacy.
conclusionsOur findings suggest that targeting LRRC15 may provide a novel strategy to augment anti-PD-1 therapy and overcome immunotherapy resistance in GBM.
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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.