ArticleCancer research2023
Tumor-Derived Small Extracellular Vesicles Inhibit the Efficacy of CAR T Cells against Solid Tumors.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 47 citations in OpenAlex.
- Extracellular vesicle proteins monitor and interfere with CLDN18.2-targeted CAR-T cell and antibody therapies against gastrointestinal cancers.Nature communications · 2026Article
- Low SLC8A1 in Colorectal Cancer Dictates Radiotherapy Resistance Through Calcium-Dependent ANXA2Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- PD-L1Biomarker research · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Combating small extracellular vesicle-mediated immunological barriers in the tumor microenvironment via strategically activatable PEGylated peptides.Signal transduction and targeted therapy · 2026Article
- Exosome-like biogenesis from the Golgi releases extracellular vesicles lacking conventional tetraspanins that mediate immune evasion in cancer.bioRxiv : the preprint server for biology · 2026Article
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- Quantification of EV-associated miRNA in liquid biopsies for biomarker signature development.Extracellular vesicles and circulating nucleic acids · 2026Review
- Review
- Target antigen-displaying extracellular vesicles boost CAR T cell efficacy in cell and mouse models of neuroblastoma.Science translational medicine · 2025Article
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- Advances of extracellular vesicles isolation and detection frontier technology: from heterogeneity analysis to clinical application.Journal of nanobiotechnology · 2025Review
- Cancer-derived extracellular vesicles in natural killer cell immune evasion: Molecular mechanisms and therapeutic insights.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Overcoming extracellular vesicle-mediated fratricide improves CAR T cell treatment against solid tumors.Nature cancer · 2025Article
- CLDN18.2 CAR-derived Extracellular Vesicle Immunotherapy Improves Outcome in Murine Pancreatic Cancer.Advanced healthcare materials · 2025Article
- Evaluating therapeutic plasma exchange and protease inhibitors as mechanisms to reduce soluble mesothelin.Scientific reports · 2025Article
- Review
- Biology of extracellular vesicles and the potential of tumor-derived vesicles for subverting immunotherapy of cancer.Journal for immunotherapy of cancer · 2025Review
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable success in the treatment of hematologic malignancies. Unfortunately, it has limited efficacy against solid tumors, even when the targeted antigens are well expressed. A better understanding of the underlying mechanisms of CAR T-cell therapy resistance in solid tumors is necessary to develop strategies to improve efficacy. Here we report that solid tumors release small extracellular vesicles (sEV) that carry both targeted tumor antigens and the immune checkpoint protein PD-L1. These sEVs acted as cell-free functional units to preferentially interact with cognate CAR T cells and efficiently inhibited their proliferation, migration, and function. In syngeneic mouse tumor models, blocking tumor sEV secretion not only boosted the infiltration and antitumor activity of CAR T cells but also improved endogenous antitumor immunity. These results suggest that solid tumors use sEVs as an active defense mechanism to resist CAR T cells and implicate tumor sEVs as a potential therapeutic target to optimize CAR T-cell therapy against solid tumors. SIGNIFICANCE: Small extracellular vesicles secreted by solid tumors inhibit CAR T cells, which provide a molecular explanation for CAR T-cell resistance and suggests that strategies targeting exosome secretion may enhance CAR T-cell efficacy. See related commentary by Ortiz-Espinosa and Srivastava, p. 2637.
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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.