ArticleJournal for immunotherapy of cancer2024
Cell membrane-anchored and tumor-targeted IL-12 T-cell therapy destroys cancer-associated fibroblasts and disrupts extracellular matrix in heterogenous osteosarcoma xenograft models.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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Who cites it
30 citing papers in PubMed, 31 citations in OpenAlex.
- Diethyl Phthalate (DEP) as a potential osteosarcoma risk factor: a multi-omics study integrating network Toxicology, single-cell RNA sequencing, and molecular docking.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Genomic landscape and tumor immune microenvironment of osteosarcoma: Bridging mechanistic insights to precision therapeutics.Bone reports · 2026Review
- TENT5A Maintains MYC mRNA Stability to Enhance Osteosarcoma Stemness.Cancer research · 2026Article
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Review
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives.iScience · 2026Review
- Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review).Oncology letters · 2026Review
- Immune exclusion as a recurrent immune-escape state driving treatment resistance in osteosarcoma: insights from single-cell, spatial, and multi-omics studies.Frontiers in immunology · 2026Review
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Targeting the osteosarcoma immune microenvironment for improved immunotherapy and translational applications.Discover oncology · 2025Review
- Collagen-disrupting attIL12 TIL therapy boosts deep T cell infiltration via dual signaling activation and CCKAR reduction in sarcomas.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- Exploring the Tumor Microenvironment in Osteosarcoma: Driver of Resistance and Progression.Cancers · 2025Review
- Article
- [Mechanism ofSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Digging Through the Complexities of Immunological Approaches in Emerging Osteosarcoma Therapeutics: A Comprehensive Narrative Review with Updated Clinical Trials.Biomedicines · 2025Review
- NGR-Modified CAF-Derived exos Targeting Tumor Vasculature to Induce Ferroptosis and Overcome Chemoresistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Association between cancer-associated fibroblasts and prognosis of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma: a bioinformatics analysis based on single-cell RNA sequencing.Cancer cell international · 2025Article
- Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming.Current oncology (Toronto, Ont.) · 2025Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarcoma.
methodIn this study, we used RNA sequencing to assess whether the recently invented membrane-anchored and tumor-targeted IL-12-armed (attIL12) T cells, which bind cell-surface vimentin (CSV) on tumor cells, could destroy CAFs to disrupt the ECM. We established an in vitro model of the interaction between osteosarcoma CAFs and attIL12-T cells to uncover the underlying mechanism by which attIL12-T cells penetrate stroma-enriched osteosarcoma tumors.
resultsRNA sequencing demonstrated that attIL12-T cell treatment altered ECM-related gene expression. Immunohistochemistry staining revealed disruption or elimination of high-density CAFs and ECM in osteosarcoma xenograft tumors following attIL12-T cell treatment, and CAF/ECM density was inversely correlated with T-cell infiltration. Other IL12-armed T cells, such as wild-type IL-12-targeted or tumor-targeted IL-12-T cells, did not disrupt the ECM because this effect depended on the engagement between CSV on the tumor cell and its ligand on the attIL12-T cells. Mechanistic studies found that attIL12-T cell treatment elevated IFNγ production on interacting with CSV
conclusionsThis study unveiled a novel therapy-attIL12-T cells-for targeting CAFs/ECM. These findings are highly relevant to humans because CAFs are abundant in human osteosarcoma.
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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.